Publications by authors named "Elisabeth Liebler-Tenorio"

35 Publications

Interferon-γ Response of subsp. Infected Goats to Recombinant and Synthetic Mycobacterial Antigens.

Front Vet Sci 2021 26;8:645251. Epub 2021 Mar 26.

Animal and Plant Health Agency, Addlestone, United Kingdom.

Despite its potential for early diagnosis of subsp. (MAP) infection, the IFN-γ release assay is not used routinely, because of low specificity of the established crude antigen preparation Johnin (PPDj). Limited data are available assessing the potential of MAP-derived protein and lipopeptide antigens to replace PPDj in assays for goats, while cattle and sheep have been studied more extensively. Furthermore, MAP infection is claimed to interfere with the diagnosis of bovine tuberculosis when other crude antigen preparations (PPDb, PPDa) are applied. In this study, the diagnostic potential of MAP-derived recombinant protein antigens, synthetic MAP lipopentapeptides and of specific peptide cocktails was assessed compared to crude mycobacterial antigen preparations in experimentally infected goats. Goats were inoculated with MAP, or subsp. (MAH) as surrogate for environmental mycobacteria, non-exposed animals served as controls. Complex-specific antibody and PPDj-induced IFN-γ responses were monitored . Infection status was assessed by pathomorphological findings and bacteriological tissue culture at necropsy 1 year after inoculation. The IFN-γ response to 13 recombinant protein antigens of MAP, two synthetic MAP lipopentapeptides and three recombinant peptide cocktails of was investigated at three defined time points after infection. At necropsy, MAP or MAH infection was confirmed in all inoculated goats, no signs of infection were found in the controls. Antibody formation was first detected 3-6 weeks post infection (wpi) in MAH-inoculated and 11-14 wpi in the MAP-inoculated goats. Maximum PPDj-induced IFN-γ levels in MAH and MAP exposed animals were recorded 3-6 and 23-26 wpi, respectively. Positive responses continued with large individual variation. Antigens Map 0210c, Map 1693c, Map 2020, Map 3651cT(it), and Map 3651c stimulated increased whole blood IFN-γ levels in several MAP-inoculated goats compared to MAH inoculated and control animals. These IFN-γ levels correlated with the intensity of the PPDj-induced responses. The two synthetic lipopentapeptides and the other MAP-derived protein antigens had no discriminatory potential. Stimulation with peptide cocktails ESAT6-CFP10, Rv3020c, and Rv3615c did not elicit IFN-γ production. Further work is required to investigate if test sensitivity will increase when mixtures of the MAP-derived protein antigens are applied.
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http://dx.doi.org/10.3389/fvets.2021.645251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034290PMC
March 2021

Chronic wasting associated with Chlamydia pneumoniae in three ex situ breeding facilities for tropical frogs.

Antonie Van Leeuwenhoek 2020 Dec 5;113(12):2139-2154. Epub 2020 Nov 5.

Chemical and Veterinary Analysis Agency Stuttgart, Schaflandstr. 3/3, 70736, Fellbach, Germany.

A number of different Chlamydia spp. have been detected in the class Amphibia with C. pneumoniae being the predominant species involved. Chlamydiae have been linked to mass mortality events, thereby representing significant pathogens that deserve attention with respect to worldwide amphibian decline. We here present six cases of chlamydiosis and asymptomatic chlamydial infections in different frog species from three ex situ amphibian conservation facilities. Clinical signs predominantly characterised by regurgitation, chronic wasting, lethargy and suspended breeding were associated with C. pneumoniae infection. Despite various treatment regimens, it was not possible to clear infections. However, intra vitam diagnostics succeeded from skin, faeces and urine for the first time.
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http://dx.doi.org/10.1007/s10482-020-01483-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716926PMC
December 2020

Regeneration of Pulmonary Tissue in a Calf Model of Fibrinonecrotic Bronchopneumonia Induced by Experimental Infection with .

Int J Mol Sci 2020 Apr 17;21(8). Epub 2020 Apr 17.

Institute for Molecular Pathogenesis, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Naumburgerstr. 96a, 07743 Jena, Germany.

Pneumonia is a cause of high morbidity and mortality in humans. Animal models are indispensable to investigate the complex cellular interactions during lung injury and repair in vivo. The time sequence of lesion development and regeneration is described after endobronchial inoculation of calves with Calves were necropsied 2-37 days after inoculation (dpi). Lesions and presence of were investigated using histology and immunohistochemistry. Calves developed bronchopneumonia at the sites of inoculation. Initially, replicated in type 1 alveolar epithelial cells followed by an influx of neutrophils, vascular leakage, fibrinous exudation, thrombosis and lobular pulmonary necrosis. Lesions were most extensive at 4 dpi. Beginning at 7 dpi, the number of chlamydial inclusions declined and proliferation of cuboidal alveolar epithelial cells and sprouting of capillaries were seen at the periphery of necrotic tissue. At 14 dpi, most of the necrosis had been replaced with alveoli lined with cuboidal epithelial cells resembling type 2 alveolar epithelial cells and mild fibrosis, and hyperplasia of organized lymphoid tissue were observed. At 37 dpi, regeneration of pulmonary tissue was nearly complete and only small foci of remodeling remained. The well-defined time course of development and regeneration of necrotizing pneumonia allows correlation of morphological findings with clinical data or treatment regimen.
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http://dx.doi.org/10.3390/ijms21082817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215337PMC
April 2020

-Infected Dendritic Cells Communicate with NK Cells via Exosomes To Activate Antibacterial Immunity.

Infect Immun 2019 12 17;88(1). Epub 2019 Dec 17.

Institute of Immunology, Friedrich Loeffler Institute, Federal Research Institute of Animal Health, Greifswald-Isle of Riems, Germany

Dendritic cells (DCs) and natural killer (NK) cells are critically involved in the early response against various bacterial microbes. Functional activation of infected DCs and NK cell-mediated gamma interferon (IFN-γ) secretion essentially contribute to the protective immunity against How DCs and NK cells cooperate during the antichlamydial response is not fully understood. Therefore, in the present study, we investigated the functional interplay between -infected DCs and NK cells. Our biochemical and cell biological experiments show that -infected DCs display enhanced exosome release. We find that such extracellular vesicles (referred to as dexosomes) do not contain infectious bacterial material but strongly induce IFN-γ production by NK cells. This directly affects growth in infected target cells. Furthermore, NK cell-released IFN-γ in cooperation with tumor necrosis factor alpha (TNF-α) and/or dexosomes augments apoptosis of both noninfected and infected epithelial cells. Thus, the combined effect of dexosomes and proinflammatory cytokines restricts growth and attenuates bacterial subversion of apoptotic host cell death. In conclusion, this provides new insights into the functional cooperation between DCs, dexosomes, and NK cells in the early steps of antichlamydial defense.
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http://dx.doi.org/10.1128/IAI.00541-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921653PMC
December 2019

Mito-xenophagic killing of bacteria is coordinated by a metabolic switch in dendritic cells.

Sci Rep 2017 06 20;7(1):3923. Epub 2017 Jun 20.

Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute of Animal Health, Südufer 10, D-17493, Greifswald, Isle of Riems, Germany.

Chlamydiae are bacterial pathogens that grow in vacuolar inclusions. Dendritic cells (DCs) disintegrate these compartments, thereby eliminating the microbes, through auto/xenophagy, which also promotes chlamydial antigen presentation via MHC I. Here, we show that TNF-α controls this pathway by driving cytosolic phospholipase (cPLA)2-mediated arachidonic acid (AA) production. AA then impairs mitochondrial function, which disturbs the development and integrity of these energy-dependent parasitic inclusions, while a simultaneous metabolic switch towards aerobic glycolysis promotes DC survival. Tubulin deacetylase/autophagy regulator HDAC6 associates with disintegrated inclusions, thereby further disrupting their subcellular localisation and stability. Bacterial remnants are decorated with defective mitochondria, mito-aggresomal structures, and components of the ubiquitin/autophagy machinery before they are degraded via mito-xenophagy. The mechanism depends on cytoprotective HSP25/27, the E3 ubiquitin ligase Parkin and HDAC6 and promotes chlamydial antigen generation for presentation on MHC I. We propose that this novel mito-xenophagic pathway linking innate and adaptive immunity is critical for effective DC-mediated anti-bacterial resistance.
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http://dx.doi.org/10.1038/s41598-017-04142-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478671PMC
June 2017

Characterization of the Protein Tyrosine Phosphatase LmPRL-1 Secreted by Leishmania major via the Exosome Pathway.

Infect Immun 2017 08 19;85(8). Epub 2017 Jul 19.

Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany

Similar to other intracellular pathogens, parasites are known to evade the antimicrobial effector functions of host immune cells. To date, however, only a few virulence factors have been described for , one of the causative agents of cutaneous leishmaniasis. Here, we have characterized the expression and function of an phosphatase, which we termed LmPRL-1. This enzyme shows a strong structural similarity to the human phosphatases of regenerating liver (PRL-1, -2, and -3) that regulate the proliferation, differentiation, and motility of cells. The biochemical characterization of the phosphatase revealed that the enzyme is redox sensitive. When analyzing the subcellular localization of LmPRL-1 in promastigotes, amastigotes, and infected macrophages, we found that the phosphatase was predominantly expressed and secreted by promastigotes via the exosome route. Finally, we observed that ectopic expression of LmPRL-1 in led to an increased number of parasites in macrophages. From these data, we conclude that the phosphatase LmPRL-1 contributes to the intracellular survival of the parasites in macrophages.
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http://dx.doi.org/10.1128/IAI.00084-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520432PMC
August 2017

Permissiveness of bovine epithelial cells from lung, intestine, placenta and udder for infection with Coxiella burnetii.

Vet Res 2017 04 12;48(1):23. Epub 2017 Apr 12.

Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut (FLI), Naumburger Strasse 96a, 07743, Jena, Germany.

Ruminants are the main source of human infections with the obligate intracellular bacterium Coxiella (C.) burnetii. Infected animals shed high numbers of C. burnetii by milk, feces, and birth products. In goats, shedding by the latter route coincides with C. burnetii replication in epithelial (trophoblast) cells of the placenta, which led us to hypothesize that epithelial cells are generally implicated in replication and shedding of C. burnetii. We therefore aimed at analyzing the interactions of C. burnetii with epithelial cells of the bovine host (1) at the entry site (lung epithelium) which govern host immune responses and (2) in epithelial cells of gut, udder and placenta decisive for the quantity of pathogen excretion. Epithelial cell lines [PS (udder), FKD-R 971 (small intestine), BCEC (maternal placenta), F3 (fetal placenta), BEL-26 (lung)] were inoculated with C. burnetii strains Nine Mile I (NMI) and NMII at different cultivation conditions. The cell lines exhibited different permissiveness for C. burnetii. While maintaining cell viability, udder cells allowed the highest replication rates with formation of large cell-filling Coxiella containing vacuoles. Intestinal cells showed an enhanced susceptibility to invasion but supported C. burnetii replication only at intermediate levels. Lung and placental cells also internalized the bacteria but in strikingly smaller numbers. In any of the epithelial cells, both Coxiella strains failed to trigger a substantial IL-1β, IL-6 and TNF-α response. Epithelial cells, with mammary epithelial cells in particular, may therefore serve as a niche for C. burnetii replication in vivo without alerting the host's immune response.
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http://dx.doi.org/10.1186/s13567-017-0430-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389005PMC
April 2017

Evaluation of associations between genotypes of Mycobacterium avium subsp. paratuberculsis and presence of intestinal lesions characteristic of paratuberculosis.

Vet Microbiol 2017 Mar 22;201:188-194. Epub 2017 Jan 22.

Friedrich-Loeffler-Institut (Federal Research Institute for Animal Health), Institute of Molecular Pathogenesis, 07743 Jena, Naumburger Str. 96a, Germany. Electronic address:

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of paratuberculosis affecting ruminants worldwide. Depending on the MAP-Type (MAP-C or MAP-S, cattle or sheep type), strains differ in virulence and host preference. There is not yet any strong evidence indicating that individual field strains of the same MAP-subgroup exhibit differences in virulence. The aim of this study was to evaluate a potential association between the genotype of individual field strains belonging to the MAP-C group and the presence of macroscopic intestinal lesions characteristic of paratuberculosis in the infected animals. 88 MAP-C isolates were sampled from clinically healthy cows at slaughter. Cows were grouped as A (n=46) with, and B (n=42) without macroscopic intestinal lesions. Sampled cows from both the A and B groups came from different farms and had a similar age distribution. MAP isolates were characterized by MIRU-VNTR and IS900-RFLP analysis. Resulting genotypes were examined for an association with the presence of macroscopic intestinal lesions characteristic of paratuberculosis. MAP isolates from groups A and B exhibited similar strain diversity: 20 and 18 combined genotypes, altogether 32 genotypes. Six of these genotypes were detected in both groups. Although no association was found between individual combined genotypes and presence of macroscopic intestinal lesions, IS900-RFLP-(BstEII)-Type-C1 (the most common type worldwide) was found more often in group A (p<0.01). The data give only weak indication for the existence of differences in virulence among MAP-cattle type isolates. Differences in the development and severity of lesions may rather depend on unknown host factors or inoculation dose. Virulence properties of IS900-RFLP-(BstEII)-Type-C1 isolates should be examined in more detail.
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http://dx.doi.org/10.1016/j.vetmic.2017.01.026DOI Listing
March 2017

Characterization of tuberculous granulomas in different stages of progression and associated tertiary lymphoid tissue in goats experimentally infected with Mycobacterium avium subsp. hominissuis.

Comp Immunol Microbiol Infect Dis 2016 Aug 26;47:41-51. Epub 2016 May 26.

Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Naumburger Str. 96a, 07743 Jena, Germany. Electronic address:

Oral infection of goats with Mycobacterium avium subsp. hominissuis (MAH) resulted in a large variety of granulomas in organized gut-associated lymphatic tissues and intestinal lymph nodes. To characterize the cellular composition of granulomas, CD4(+), CD8(+), γδ, B lymphocytes and plasma, CD25(+), CD68(+), MHC-II(+), Ki67(+) and endothelial cells were labeled in consecutive frozen sections by immunohistochemistry and acid fast bacilli (AFB) by Kinyoun stain. Granulomas with extensive necrosis, little mineralization and variable numbers of AFB surrounded by many CD4(+) T cells, but only few epitheloid macrophages were observed in severely sick goats at 2-3mpi. They were interpreted as exuberant immune reaction. Organized granulomas with very few AFB were seen in clinically healthy goats at 13mpi. The necrotic cores were surrounded by a zone of granulomatous infiltrate with many epitheloid macrophages and few lymphocytes. This zone was initially wide and highly vascularized and became progressively smaller. It was enclosed by an increasing layer of connective tissue. All organized granulomas were surrounded by compartimentalized tertiary lymphoid tissue. The granulomas in experimental infection of goats with MAH reflect the heterogeneity of lesions seen in mycobacterial infections of humans and ruminants and are therefore valuable for comparative research.
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http://dx.doi.org/10.1016/j.cimid.2016.05.006DOI Listing
August 2016

LAMP proteins account for the maturation delay during the establishment of the Coxiella burnetii-containing vacuole.

Cell Microbiol 2016 Feb 25;18(2):181-94. Epub 2015 Sep 25.

Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Germany.

The obligate intracellular pathogen Coxiella burnetii replicates in a large phagolysosomal-like vacuole. Currently, both host and bacterial factors required for creating this replicative parasitophorous C. burnetii-containing vacuole (PV) are poorly defined. Here, we assessed the contributions of the most abundant proteins of the lysosomal membrane, LAMP-1 and LAMP-2, to the establishment and maintenance of the PV. Whereas these proteins were not critical for uptake of C. burnetii, they influenced the intracellular replication of C. burnetii. In LAMP-1/2 double-deficient fibroblasts as well as in LAMP-1/2 knock-down cells, C. burnetii establishes a significantly smaller, yet faster maturing vacuole, which harboured more bacteria. The accelerated maturation of PVs in LAMP double-deficient fibroblasts, which was partially or fully reversed by ectopic expression of LAMP-1 or LAMP-2, respectively, was characterized by an increased fusion rate with endosomes, lysosomes and bead-containing phagosomes, but not by different fusion kinetics with autophagy vesicles. These findings establish that LAMP proteins are critical for the maturation delay of PVs. Unexpectedly, neither the creation of the spacious vacuole nor the delay in maturation was found to be prerequisites for the intracellular replication of C. burnetii.
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http://dx.doi.org/10.1111/cmi.12494DOI Listing
February 2016

Characterization of a caprine model for the subclinical initial phase of Mycobacterium avium subsp. paratuberculosis infection.

BMC Vet Res 2015 Mar 24;11:74. Epub 2015 Mar 24.

Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Jena, Germany.

Background: Paratuberculosis caused by Mycobacterium avium subsp. paratuberculosis (MAP) is difficult to control due to a long phase of clinically non-apparent (latent) infection for which sensitive diagnostics are lacking. A defined animal model for this phase of the infection can help to investigate host-MAP interactions in apparently healthy animals and identify surrogate markers for disease progress and might also serve as challenge model for vaccines. To establish such a model in goats, different age at inoculation and doses of oral inoculum of MAP were compared. Clinical signs, faecal shedding as well as MAP-specific antibody, IFN-γ and IL-10 responses were used for in vivo monitoring. At necropsy, about one year after inoculation (pi), pathomorphological findings and bacterial organ burden (BOB) were scored.

Results: MAP infection manifested in 26/27 inoculated animals irrespective of age at inoculation and dose. Clinical signs developed in three goats. Faecal shedding, IFN-γ and antibody responses emerged 6, 10-14 and 14 wpi, respectively, and continued with large inter-individual variation. One year pi, lesions were detected in 26 and MAP was cultured from tissues of 23 goats. Positive animals subdivided in those with high and low overall BOB. Intestinal findings resembled paucibacillary lesions in 23 and multibacillary in 4 goats. Caseous and calcified granulomas predominated in intestinal LNN. BOB and lesion score corresponded well in intestinal mucosa and oGALT but not in intestinal LNN.

Conclusions: A defined experimental infection model for the clinically non-apparent phase of paratuberculosis was established in goats as suitable basis for future studies.
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http://dx.doi.org/10.1186/s12917-015-0381-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404677PMC
March 2015

Enrofloxacin and macrolides alone or in combination with rifampicin as antimicrobial treatment in a bovine model of acute Chlamydia psittaci infection.

PLoS One 2015 13;10(3):e0119736. Epub 2015 Mar 13.

Institute of Molecular Pathogenesis at Friedrich-Loeffler-Institut (Federal Research Institute for Animal Health), Naumburger Str. 96a, 07743 Jena, Germany.

Chlamydia psittaci is a zoonotic bacterium with a wide host range that can cause respiratory disease in humans and cattle. In the present study, effects of treatment with macrolides and quinolones applied alone or in combination with rifampicin were tested in a previously established bovine model of respiratory C. psittaci infection. Fifty animals were inoculated intrabronchially at the age of 6-8 weeks. Seven served as untreated controls, the others were assigned to seven treatment groups: (i) rifampicin, (ii) enrofloxacin, (iii) enrofloxacin + rifampicin, (iv) azithromycin, (v) azithromycin + rifampicin, (vi) erythromycin, and (vii) erythromycin + rifampicin. Treatment started 30 hours after inoculation and continued until 14 days after inoculation (dpi), when all animals were necropsied. The infection was successful in all animals and sufficient antibiotic levels were detected in blood plasma and tissue of the treated animals. Reisolation of the pathogen was achieved more often from untreated animals than from other groups. Nevertheless, pathogen detection by PCR was possible to the same extent in all animals and there were no significant differences between treated and untreated animals in terms of local (i.e., cell count and differentiation of BALF-cells) and systemic inflammation (i.e. white blood cells and concentration of acute phase protein LBP), clinical signs, and pathological findings at necropsy. Regardless of the reduced reisolation rate in treated animals, the treatment of experimentally induced respiratory C. psittaci infection with enrofloxacin, azithromycin or erythromycin alone or in combination with rifampicin was without obvious benefit for the host, since no significant differences in clinical and pathological findings or inflammatory parameters were detected and all animals recovered clinically within two weeks.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0119736PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358964PMC
January 2016

Evaluation of antimicrobial treatment in a bovine model of acute Chlamydia psittaci infection: tetracycline versus tetracycline plus rifampicin.

Pathog Dis 2015 Feb 30;73(1):1-12. Epub 2015 Jan 30.

Institute of Molecular Pathogenesis at Friedrich-Loeffler-Institut (Federal Research Institute for Animal Health), Jena, Germany

Antimicrobial treatment of chlamydial infections is known to be of limited efficacy. In this study, effects of doxycycline (D), usually the drug of choice, were compared with the combined therapy of doxycycline and rifampicin (R) in a bovine model of respiratory Chlamydia psittaci infection. After intrabronchial inoculation of the pathogen, 30 animals were assigned to five groups (n = 6 per group): untreated controls, monotherapy with D (5 mg kg(-1)day(-1) or 10 mg kg(-1)day(-1)), and combination therapy of D and R (600 mg day(-1)). Treatment continued until day 14 post inoculation (d.p.i.). Clinical signs, inflammatory markers, and pathological findings confirmed successful infection in all animals. Reisolation of the pathogen was possible in 4/6 untreated animals and in 4/12 animals treated with D alone until 4 d.p.i., but in none of the calves of the two D + R groups. Pathogen detection was possible in all animals without significant differences among groups. Severity of disease and time course of its resolution, assessed by clinical and pathological findings as well as inflammatory parameters, were not significantly different between untreated controls and calves receiving D alone or in combination with R. Regardless of the treatment regimen, all groups recovered clinically and cleared the infection within 2 weeks.
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http://dx.doi.org/10.1111/2049-632X.12212DOI Listing
February 2015

Chlamydia psittaci: new insights into genomic diversity, clinical pathology, host-pathogen interaction and anti-bacterial immunity.

Int J Med Microbiol 2014 Oct 28;304(7):877-93. Epub 2014 Jun 28.

Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, Jena, Germany. Electronic address:

The distinctive and unique features of the avian and mammalian zoonotic pathogen Chlamydia (C.) psittaci include the fulminant course of clinical disease, the remarkably wide host range and the high proportion of latent infections that are not leading to overt disease. Current knowledge on associated diseases is rather poor, even in comparison to other chlamydial agents. In the present paper, we explain and summarize the major findings of a national research network that focused on the elucidation of host-pathogen interactions in vitro and in animal models of C. psittaci infection, with the objective of improving our understanding of genomics, pathology, pathophysiology, molecular pathogenesis and immunology, and conceiving new approaches to therapy. We discuss new findings on comparative genome analysis, the complexity of pathophysiological interactions and systemic consequences, local immune response, the role of the complement system and antigen presentation pathways in the general context of state-of-the-art knowledge on chlamydial infections in humans and animals and single out relevant research topics to fill remaining knowledge gaps on this important yet somewhat neglected pathogen.
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http://dx.doi.org/10.1016/j.ijmm.2014.06.010DOI Listing
October 2014

A bovine model of a respiratory Parachlamydia acanthamoebae infection.

Pathog Dis 2015 Feb 30;73(1):1-14. Epub 2015 Jan 30.

Institute of Molecular Pathogenesis at Friedrich-Loeffler-Institut (Federal Research Institute for Animal Health), Jena, Germany

The aim of this study was to evaluate the pathogenicity of Parachlamydia (P.) acanthamoebae as a potential agent of lower respiratory tract disease in a bovine model of induced lung infection. Intrabronchial inoculation with P. acanthamoebae was performed in healthy calves aged 2-3 months using two challenge doses: 10(8) and 10(10) bacteria per animal. Controls received 10(8) heat-inactivated bacteria. Challenge with 10(8) viable Parachlamydia resulted in a mild degree of general indisposition, whereas 10(10) bacteria induced a more severe respiratory illness becoming apparent 1-2 days post inoculation (dpi), affecting 9/9 (100%) animals and lasting for 6 days. The extent of macroscopic pulmonary lesions was as high as 6.6 (6.0)% [median (range)] of lung tissue at 2-4 dpi and correlated with parachlamydial genomic copy numbers detected by PCR, and with bacterial load estimated by immunohistochemistry in lung tissue. Clinical outcome, acute phase reactants, pathological findings and bacterial load exhibited an initial dose-dependent effect on severity. Animals fully recovered from clinical signs of respiratory disease within 5 days. The bovine lung was shown to be moderately susceptible to P. acanthamoebae, exhibiting a transient pneumonic inflammation after intrabronchial challenge. Further studies are warranted to determine the precise pathophysiologic pathways of host-pathogen interaction.
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http://dx.doi.org/10.1111/2049-632X.12201DOI Listing
February 2015

Evidence for the existence of two new members of the family Chlamydiaceae and proposal of Chlamydia avium sp. nov. and Chlamydia gallinacea sp. nov.

Syst Appl Microbiol 2014 Mar 22;37(2):79-88. Epub 2014 Jan 22.

Faculty of Mathematics and Computer Science, Friedrich-Schiller-Universität, Jena, Germany.

The family Chlamydiaceae with the recombined single genus Chlamydia currently comprises nine species, all of which are obligate intracellular organisms distinguished by a unique biphasic developmental cycle. Anecdotal evidence from epidemiological surveys in flocks of poultry, pigeons and psittacine birds have indicated the presence of non-classified chlamydial strains, some of which may act as pathogens. In the present study, phylogenetic analysis of ribosomal RNA and ompA genes, as well as multi-locus sequence analysis of 11 field isolates were conducted. All independent analyses assigned the strains into two different clades of monophyletic origin corresponding to pigeon and psittacine strains or poultry isolates, respectively. Comparative genome analysis involving the type strains of currently accepted Chlamydiaceae species and the designated type strains representing the two new clades confirmed that the latter could be classified into two different species as their average nucleotide identity (ANI) values were always below 94%, both with the closest relative species and between themselves. In view of the evidence obtained from the analyses, we propose the addition of two new species to the current classification: Chlamydia avium sp. nov. comprising strains from pigeons and psittacine birds (type strain 10DC88(T); DSMZ: DSM27005(T), CSUR: P3508(T)) and Chlamydia gallinacea sp. nov. comprising strains from poultry (type strain 08-1274/3(T); DSMZ: DSM27451(T), CSUR: P3509(T)).
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http://dx.doi.org/10.1016/j.syapm.2013.12.004DOI Listing
March 2014

Mycoplasma feriruminatoris sp. nov., a fast growing Mycoplasma species isolated from wild Caprinae.

Syst Appl Microbiol 2013 Dec 6;36(8):533-8. Epub 2013 Sep 6.

International Livestock Research Institute, PO Box 30709, 00100 Nairobi, Kenya. Electronic address:

Five Mycoplasma strains from wild Caprinae were analyzed: four from Alpine ibex (Capra ibex) which died at the Berlin Zoo between 1993 and 1994, one from a Rocky Mountain goat collected in the USA prior to 1987. These five strains represented a population different from the populations belonging to the 'Mycoplasma mycoides cluster' as tested using multi locus sequence typing, Matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis and DNA-DNA hybridization. Analysis of the 16S rRNA gene (rrs), genomic sequence based in silico as well as laboratory DNA-DNA hybridization, and the analysis of phenotypic traits in particular their exceptionally rapid growth all confirmed that they do not belong to any Mycoplasma species described to date. We therefore suggest these strains represent a novel species, for which we propose the name Mycoplasma feriruminatoris sp. nov. The type strain is G5847(T) (=DSM 26019(T)=NCTC 13622(T)) [corrected].
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http://dx.doi.org/10.1016/j.syapm.2013.07.005DOI Listing
December 2013

Amphisomal route of MHC class I cross-presentation in bacteria-infected dendritic cells.

J Immunol 2013 Mar 15;190(6):2791-806. Epub 2013 Feb 15.

Institute of Immunology, Federal Research Institute for Animal Health, Friedrich-Loeffler-Institute, 17493 Greifswald-Isle of Riems, Germany.

Dendritic cells (DCs) are among the first professional APCs encountered by the obligate intracellular bacterium Chlamydia during infection. Using an established mouse bone marrow-derived DC line, we show that DCs control chlamydial infection in multiple small inclusions characterized by restricted bacterial growth, impaired cytosolic export of the virulence factor chlamydial protease-like activity factor, and interaction with guanylate-binding protein 1, a host cell factor involved in the initiation of autophagy. During maturation of infected DCs, chlamydial inclusions disintegrate, likely because they lack chlamydial protease-like activity factor-mediated protection. Released cytosolic Chlamydia are taken up by autophagosomes and colocalize with cathepsin-positive amphisomal vacuoles, to which peptide transporter TAP and upregulated MHC class I (MHC I) are recruited. Chlamydial Ags are subsequently generated through routes involving preprocessing in amphisomes via cathepsins and entry into the cytosol for further processing by the proteasome. Finally, bacterial peptides are reimported into the endosomal pathway for loading onto recycling MHC I. Thus, we unravel a novel pathway of MHC I-mediated cross-presentation that is initiated with a host cellular attack physically disrupting the parasitophorous vacuole, involves autophagy to collect cytosolic organisms into autophagosomes, and concludes with complex multistep antigenic processing in separate cellular compartments.
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http://dx.doi.org/10.4049/jimmunol.1202741DOI Listing
March 2013

A bovine model of respiratory Chlamydia psittaci infection: challenge dose titration.

PLoS One 2012 27;7(1):e30125. Epub 2012 Jan 27.

Institute of Molecular Pathogenesis at 'Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Jena, Germany.

This study aimed to establish and evaluate a bovine respiratory model of experimentally induced acute C. psittaci infection. Calves are natural hosts and pathogenesis may resemble the situation in humans. Intrabronchial inoculation of C. psittaci strain DC15 was performed in calves aged 2-3 months via bronchoscope at four different challenge doses from 10(6) to 10(9) inclusion-forming units (ifu) per animal. Control groups received either UV-inactivated C. psittaci or cell culture medium. While 10(6) ifu/calf resulted in a mild respiratory infection only, the doses of 10(7) and 10(8) induced fever, tachypnea, dry cough, and tachycardia that became apparent 2-3 days post inoculation (dpi) and lasted for about one week. In calves exposed to 10(9) ifu C. psittaci, the respiratory disease was accompanied by severe systemic illness (apathy, tremor, markedly reduced appetite). At the time point of most pronounced clinical signs (3 dpi) the extent of lung lesions was below 10% of pulmonary tissue in calves inoculated with 10(6) and 10(7) ifu, about 15% in calves inoculated with 10(8) and more than 30% in calves inoculated with 10(9) ifu C. psittaci. Beside clinical signs and pathologic lesions, the bacterial load of lung tissue and markers of pulmonary inflammation (i.e., cell counts, concentration of proteins and eicosanoids in broncho-alveolar lavage fluid) were positively associated with ifu of viable C. psittaci. While any effect of endotoxin has been ruled out, all effects could be attributed to infection by the replicating bacteria. In conclusion, the calf represents a suitable model of respiratory chlamydial infection. Dose titration revealed that both clinically latent and clinically manifest infection can be reproduced experimentally by either 10(6) or 10(8) ifu/calf of C. psittaci DC15 while doses above 10(8) ifu C. psittaci cannot be recommended for further studies for ethical reasons. This defined model of different clinical expressions of chlamydial infection allows studying host-pathogen interactions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0030125PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267716PMC
July 2012

Persistent Chlamydia trachomatis infection of HeLa cells mediates apoptosis resistance through a Chlamydia protease-like activity factor-independent mechanism and induces high mobility group box 1 release.

Infect Immun 2012 Jan 24;80(1):195-205. Epub 2011 Oct 24.

Institute of Medical Microbiology, Clinic for Anesthesiology and Intensive Care Medicine, Friedrich Schiller University of Jena, Jena, Germany.

Intracellular persistence of Chlamydia trachomatis has been implicated in the development of chronic infection that can result in pelvic inflammatory disease and tubal sterility. By inhibition of host cell apoptosis, chlamydiae have evolved a strategy to maintain the intracellular environment for replication and persistence. Both antiapoptotic host cell-derived factors and the chlamydial protease-like activity factor (CPAF) are involved in Chlamydia-mediated apoptosis resistance. Here, we show that in HeLa cells infected with gamma interferon (IFN-γ)-induced persistent C. trachomatis serovar D, the expression of CPAF is downregulated, and proapoptotic protease substrates are not cleaved. Persistent infection protected HeLa cells from apoptosis when they were exposed to staurosporine. Small-interfering RNA-mediated inhibition of myeloid cell leukemia 1 (Mcl-1) protein upregulation sensitized persistently infected cells for apoptosis. The inhibitor of apoptosis protein 2 (IAP-2) seems not to be relevant in this context because IAP-2 protein was not induced in response to IFN-γ treatment. Although apoptosis was inhibited, persistent infection caused cell membrane disintegration, as measured by the increased release of cytokeratin 18 from HeLa cells. Moreover, persistently infected cells released significantly increased amounts of high mobility group box 1 (HMGB1) protein which represents a proinflammatory damage-associated pattern molecule. The data of this study suggest that cells infected with persistent C. trachomatis are protected from apoptosis independently of CPAF but may promote chronic inflammation through HMGB1 release.
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http://dx.doi.org/10.1128/IAI.05619-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255666PMC
January 2012

Infection of calves with bovine norovirus GIII.1 strain Jena virus: an experimental model to study the pathogenesis of norovirus infection.

J Virol 2011 Nov 31;85(22):12013-21. Epub 2011 Aug 31.

Friedrich Loeffler Institute, Federal Research Institute for Animal Health, Institute for Molecular Pathogenesis, Naumburger Strasse 96a, 07743 Jena, Germany.

The experimental infection of newborn calves with bovine norovirus was used as a homologous large animal model to study the pathogenesis of norovirus infection and to determine target cells for viral replication. Six newborn calves were inoculated orally with Jena virus (JV), a bovine norovirus GIII.1 strain, and six calves served as mock-inoculated controls. Following infection, calves were euthanized before the onset of diarrhea (12 h postinoculation [hpi]), shortly after the onset of diarrhea (18 to 21 hpi), and postconvalescence (4 days pi [dpi]). Calves inoculated with JV developed severe watery diarrhea at 14 to 16 hpi, and this symptom lasted for 53.5 to 67.0 h. Intestinal lesions were characterized by severe villus atrophy together with loss and attenuation of villus epithelium. Viral capsid antigen (JV antigen) was detected by immunohistochemistry in the cytoplasm of epithelial cells on villi. In addition, granular material positive for JV antigen was detected in the lamina propria of villi. Lesions first appeared at 12 hpi and were most extensive at 18 to 19 hpi, extending from midjejunum to ileum. The intestinal mucosa had completely recovered at 4 dpi. There was no indication of systemic infection as described for norovirus infection in mice. JV was found in intestinal contents by reverse transcription-PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) as early as 12 hpi. Fecal shedding of the virus started at 13 hpi and stopped at 23 hpi or at necropsy (4 dpi), respectively. Throughout the trial, none of the control calves tested positive for JV by ELISA or RT-PCR.
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http://dx.doi.org/10.1128/JVI.05342-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209315PMC
November 2011

Chronic intestinal Mycobacteria infection: discrimination via VOC analysis in exhaled breath and headspace of feces using differential ion mobility spectrometry.

J Breath Res 2011 Jun 21;5(2):027103. Epub 2011 Apr 21.

Institute of Molecular Pathogenesis at the 'Friedrich-Loeffler-Institut' (Federal Research Institute for Animal Health), Jena, Germany.

Differential ion mobility spectrometry (DMS) is a method to detect volatile organic compounds (VOC) in the ppt range. This study assessed whether VOC analysis using DMS could discriminate subjects with an experimentally induced chronic intestinal infection caused by Mycobacteria from non-infected controls. The animal model consisted of two groups of goats orally infected with two different doses of Mycobacterium avium subspecies paratuberculosis (MAP) and one group of non-infected healthy controls (each group: n = 6). Using DMS, exhaled breath and headspace of feces were analyzed on-line on an individual basis 9 months after inoculation of MAP. Data analysis included peak detection, cluster analysis, selection of discriminating VOC features (Mann-Whitney U test), and classification using a support-vector-machine. Taking the background of ambient air conditions into account, VOC analysis of exhaled breath as well as of feces revealed significant differences between chronically infected animals and non-infected controls. In both specimens, increasing as well as decreasing VOC features could be attributed to infection. Discrimination between infected and non-infected animals was sharper analyzing exhaled breath compared to headspace of feces. In exhaled breath, at least two VOC features were found to increase in a dose-dependent manner with increasing doses of MAP inoculated. Results of this study provide strong evidence that DMS analysis of exhaled breath has the potential to become a valuable tool for non-invasive assessment of VOC specifically related to certain diseases or infections.
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http://dx.doi.org/10.1088/1752-7155/5/2/027103DOI Listing
June 2011

Recurrence of Chlamydiasuis infection in pigs after short-term antimicrobial treatment.

Vet J 2011 Mar 25;187(3):405-7. Epub 2010 Aug 25.

Institute of Molecular Pathogenesis in the Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Naumburger Str 96a, 07743 Jena, Germany.

The effect of short-term antimicrobial treatment on natural excretion of Chlamydia suis in rectal swabs and C. suis and Chlamydophila psittaci in nasal swabs was investigated in 47 clinically normal piglets by quantitative real-time PCR. Pigs were treated IM with 4 mg/kg enrofloxacin for 5 days (n = 22) or 2.5mg/kg enrofloxacin for 3 days followed by 100mg/mL tiamulin (n = 25). Antimicrobial treatment reduced the number of pigs positive for chlamydiae and the quantity of chlamydial DNA in positive swabs for a few days, but chlamydial excretion recurred in both groups. Short-term antimicrobial treatment at dosages recommended for treatment of other bacterial infections in pig herds was not effective in eliminating naturally occurring subclinical chlamydial infection in pigs.
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http://dx.doi.org/10.1016/j.tvjl.2010.01.008DOI Listing
March 2011

Respiratory function and pulmonary lesions in pigs infected with porcine reproductive and respiratory syndrome virus.

Vet J 2011 Mar 20;187(3):310-9. Epub 2010 Jan 20.

Institute of Molecular Pathogenesis in the Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Naumburger Str 96a, 07743 Jena, Germany.

Pulmonary dysfunction was evaluated in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV, isolate VR-2332) and compared to clinical and pathological findings. Infected pigs developed fever, reduced appetite, respiratory distress and dullness at 9 days post-inoculation (dpi). Non-invasive pulmonary function tests using impulse oscillometry and rebreathing of test gases (He, CO) revealed peripheral airway obstruction, reduced lung compliance and reduced lung CO-transfer factor. PRRSV-induced pulmonary dysfunction was most marked at 9-18 dpi and was accompanied by a significantly increased respiratory rate and decreased tidal volume. Expiration was affected more than inspiration. On histopathological examination, multifocal areas of interstitial pneumonia (more severe and extensive at 10 dpi than 21 dpi) were identified as a possible structural basis for reduced lung compliance and gas exchange disturbances.
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http://dx.doi.org/10.1016/j.tvjl.2009.12.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7128265PMC
March 2011

A clinically silent respiratory infection with Chlamydophila spp. in calves is associated with airway obstruction and pulmonary inflammation.

Vet Res 2007 Sep-Oct;38(5):711-28. Epub 2007 Jul 10.

Institute of Molecular Pathogenesis in the Friedrich-Loeffler-Institute (Federal Research Institute for Animal Health), Naumburger Str. 96a, 07743 Jena, Germany.

This study was aimed at evaluating functional and inflammatory consequences of persistent chlamydial infections on the respiratory system in clinically inconspicuous calves aged 2-7 months. Thirteen calves persistently infected with Chlamydophila (C.) abortus and/or C. pecorum (Chl+) were compared to 12 calves without chlamydial infections (Chl-). In order to evaluate lung function, 36 non-invasive impulse oscillometry tests were performed per animal within 6 months. The group of chronically infected animals was distinguished by significantly higher peripheral airway resistance (indicating peripheral airway obstruction), significantly higher respiratory rates, and significantly higher minute volumes of ventilation. At the age of seven months, all calves were necropsied, broncho-alveolar lavage fluid (BALF) was obtained ex vivo, and lungs were examined histologically. Significantly higher concentrations of total protein and 8-iso-prostane (8-IP), as well as higher activities of matrix metalloprotease 2 were measured in BALF samples of Chl+ calves. Histologically, markedly activated bronchus-associated lymphoid tissue (BALT) causing partial obstruction of bronchiolar lumina was found in the apical pulmonary lobes of Chl+ calves. Chlamydial DNA was detected in the lung tissue of 7 out of 13 Chl+ calves by real-time PCR. In conclusion, respiratory chlamydial infection appeared to be associated with chronic inflammation of the lungs and airways. Despite the lack of clinical symptoms, pulmonary dysfunctions persisted in calves until the age of seven months. Data obtained in this study provide new insight illustrating the impact of nearly ubiquitous subclinical infections on the respiratory system.
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http://dx.doi.org/10.1051/vetres:2007027DOI Listing
November 2007

Tickborne encephalitis in naturally exposed monkey (Macaca sylvanus).

Emerg Infect Dis 2007 Jun;13(6):905-7

Friedrich-Loeffler-Institute, Jena, Germany.

We describe tickborne encephalitis (TBE) in a monkey (Macaca sylvanus) after natural exposure in an area at risk for TBE. TBE virus was present in the brain and could be identified as closely related to the European subtype, strain Neudoerfl.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2792843PMC
http://dx.doi.org/10.3201/eid1306.061173DOI Listing
June 2007

Impact of latent infections with Chlamydophila species in young cattle.

Vet J 2008 Feb 21;175(2):202-11. Epub 2007 Feb 21.

Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institute (FLI), Naumburger Street 96 a, 07743 Jena, Germany.

To assess long-term effects of naturally occurring infection with Chlamydophila spp. on animal health, 25 calves were grouped according to their chlamydial carrier status and checked for health parameters from 2 to 7 months of age. Monthly PCR testing revealed persistent or frequently recurring infections with Chlamydophila pecorum and Chlamydophila abortus in Group 2 (Chl+, n=13), but not in Group 1 (Chl-, n=12). Despite the absence of any clinical illness, calves in Group 2 showed significantly higher body temperatures (subfebrile), lower bodyweights, reduced serum iron concentrations, lower total haemoglobin and haematocrit values. Counting and flow cytometric differentiation of peripheral white blood cells revealed a general decrease in leukocytes in Group 2. At necropsy, follicular bronchiolitis was found in 10/13 calves in Group 2 but in none of Group 1, and the weight of pharyngeal tonsils was significantly higher in Group 2. In conclusion, naturally occurring infections with Chlamydophila species in calves were found to be associated with chronic effects on animal health at a subclinical level.
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http://dx.doi.org/10.1016/j.tvjl.2007.01.004DOI Listing
February 2008

Detection of rotaviruses and intestinal lesions in broiler chicks from flocks with runting and stunting syndrome (RSS).

Avian Dis 2006 Sep;50(3):411-8

Institute of Bacterial Infections and Zoonoses, Federal Research Institute for Animal Health, Jena, Germany.

The intestinal tract and intestinal contents were collected from 34 stunted, 5-to-14-day-old broiler chicks from eight flocks with runting and stunting syndrome (RSS) in Northern Germany to investigate intestinal lesions and the presence of enteric pathogens with a special focus on rotaviruses (RVs). Seven chicks from a healthy flock were used as controls. Severe villous atrophy was seen in chicks from six flocks with RSS but not in the control flock. Lesions were often "regionally" distributed in the middle-to-distal small intestine. Transmission electron microscopy (TEM), polyacrylamide-gel electrophoresis (PAGE), reverse-transcriptase polymerase chain reaction (RT-PCR), and seminested RT-PCR were used for detection and characterization of RVs. The PAGE allows discrimination of different RV groups, and the RT-PCR was used to verify the presence of group (gp) A RVs. RVs were detected (by all methods) in 32 of 34 chicks from the flocks with RSS. By TEM (negative staining), RV particles were observed in intestinal contents of 28 chicks from the flocks with RSS. PAGE analysis showed four RV groups: gpA, gpD, gpF, and gpG. Group A RVs were detected in four chicks from two flocks with RSS, without intestinal lesions. GpD RVs were detected in 12 chicks of five flocks with RSS, 10 of them with severe villous atrophy. GpF RVs were confirmed in four chicks from three flocks with RSS and in two birds in the control flock. GpG RVs were verified in two chicks from two flocks with RSS, one with, and one without, intestinal lesions. At present, PCR methods are only available for detection of gpA RVs. Using RT-PCR, gpA RVs were identified in samples from 22 chicks including samples of two chicks from the control flock. Statistical analysis revealed a positive correlation between presence of gpD RV and severe villous atrophy in flocks with RSS. The results suggest that gpD RV plays a major role in the pathogenesis of RSS.
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http://dx.doi.org/10.1637/7511-020106R.1DOI Listing
September 2006

Transcriptional response patterns of Chlamydophila psittaci in different in vitro models of persistent infection.

Infect Immun 2006 Aug;74(8):4801-8

Institute of Bacterial Infections and Zoonoses, Friedrich-Loeffler-Institut (Federal Research Institute for Animal Health), Jena, Germany.

The obligatory intracellular bacterium Chlamydophila psittaci is the causative agent of psittacosis in birds and humans. The capability of this zoonotic pathogen to develop a persistent phase is likely to play a role in chronicity of infections, as well as in failure of antibiotic therapy and immunoprophylaxis. To elucidate three different in vitro models for transition of C. psittaci to persistence (iron depletion, penicillin G treatment, and gamma interferon [IFN-gamma] exposure), a set of 27 genes was examined by mRNA expression analysis using quantitative real-time PCR. While the phenotypical characteristics were the same as in other chlamydiae, i.e., aberrant morphology of reticulate bodies, loss of cultivability, and rescue of infectivity upon removal of inducers, the transcriptional response of C. psittaci to persistence-inducing factors included several new and distinctive features. Consistent downregulation of membrane proteins, chlamydial sigma factors, cell division protein, and reticulate body-elementary body differentiation proteins from 24 h postinfection onward proved to be a general feature of C. psittaci persistence. However, other genes displayed considerable variations in response patterns from one model to another, which suggests that there is no persistence model per se. In contrast to results for Chlamydia trachomatis, late shutdown of essential genes in C. psittaci was more comprehensive with IFN-gamma-induced persistence, which is probably due to the absence of a functional tryptophan synthesis operon.
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http://dx.doi.org/10.1128/IAI.01487-05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1539575PMC
August 2006

MALT structure and function in farm animals.

Vet Res 2006 May-Jun;37(3):257-80. Epub 2006 Feb 23.

Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Naumburger Str. 96 a, 07743 Jena, Germany.

Mucosa-associated lymphoid tissue (MALT) is defined as an organized lymphoid tissue in the mucosa that samples antigens. The morphological characteristics that distinguish MALT from lymphoid infiltrates are discussed. MALT has been extensively investigated in laboratory animals, while knowledge in cattle, sheep, goats, pigs and horses that are summarized under the term farm animals in this review is fragmentary. Literature data about the distribution, morphology, function and involvement in infectious diseases of MALT in farm animals are described. The understanding of specific features of MALT in other species than laboratory animals is important for comparative research, in order to understand pathological and immunological processes in the respective species and as a potential route of vaccination of mucosal surfaces.
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http://dx.doi.org/10.1051/vetres:2006001DOI Listing
June 2006