Publications by authors named "Luis Donis-Maturano"

15 Publications

  • Page 1 of 1

Outer Membrane Vesicles From Modulate Immune Response and Induce Cytoskeleton Rearrangement in Peripheral Blood Mononuclear Cells.

Front Microbiol 2020 19;11:556795. Epub 2020 Oct 19.

Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico.

Similar to what has been described in other Gram-negative bacteria, releases outer membrane vesicles (OMVs). OMVs from 16M and the rough-mutant VTRM1 were able to induce a protective immune response against virulent in mice models. The presence of some proteins which had previously been reported to induce protection against were found in the proteome of OMVs from 16M. However, the proteome of OMVs from VTRM1 had not previously been determined. In order to be better understand the role of OMVs in host-cell interactions, the aim of this work was to compare the proteomes of OMVs from 16M and the derived rough-mutant VTRM1, as well as to characterize the immune response induced by vesicles on host cells. Additionally, the effect of SDS and proteinase K on the stability of OMVs was analyzed. OMVs from 16M (smooth strain) and the VTRM1 rough mutant (lacking the -polysaccharide side chain) were analyzed through liquid chromatography-mass spectrometry (LC-MS/MS). OMVs were treated with proteinase K, sodium deoxycholate, and SDS, and then their protein profile was determined using SDS-PAGE. Furthermore, PBMCs were treated with OMVs in order to measure their effect on cytoskeleton, surface molecules, apoptosis, DNA damage, proliferation, and cytokine-induction. A total of 131 proteins were identified in OMVs from 16M, and 43 in OMVs from VTRM1. Proteome comparison showed that 22 orthologous proteins were common in vesicles from both strains, and their core proteome contained Omp31, Omp25, GroL, and Omp16. After a subsequent detergent and enzyme treatment, OMVs from VTRM1 exhibited higher sensitive compared to OMVs from the 16M strain. Neither OMVs induced IL-17, proliferation, apoptosis or DNA damage. Nonetheless, OMVs from the smooth and rough strains induced overproduction of TNFα and IL-6, as well as actin and tubulin rearrangements in the cytoskeleton. Moreover, OMVs from both strains inhibited PD-L1 expression in T-cells. These data revealed significant differences in OMVs derived from the rough and smooth strains, among which, the presence or absence of complete LPS appeared to be crucial to protect proteins contained within vesicles and to drive the immune response.
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http://dx.doi.org/10.3389/fmicb.2020.556795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604303PMC
October 2020

Langerhans Cells From Mice at Birth Express Endocytic- and Pattern Recognition-Receptors, Migrate to Draining Lymph Nodes Ferrying Antigen and Activate Neonatal T Cells .

Front Immunol 2020 27;11:744. Epub 2020 Apr 27.

Department of Cell Biology, Center for Advanced Research, The National Polytechnic Institute, Cinvestav-IPN, Mexico City, Mexico.

Antigen capturing at the periphery is one of the earliest, crucial functions of antigen-presenting cells (APCs) to initiate immune responses. Langerhans cells (LCs), the epidermal APCs migrate to draining lymph nodes (DLNs) upon acquiring antigens. An arsenal of endocytic molecules is available to this end, including lectins and pathogen recognition receptors (PRRs). However, cutaneous LCs are poorly defined in the early neonatal period. We assessed endocytic molecules expression : Mannose (CD206)-, Scavenger (SRA/CD204)-, Complement (CD2l, CDllb)-, and Fc-Receptors (CD16/32, CD23) as well as CD1d, CD14, CD205, Langerin (CD207), MHCII, and TLR4 in unperturbed epidermal LCs from both adult and early neonatal mice. As most of these markers were negative at birth (day 0), LC presence was revealed with the conspicuous, epidermal LC-restricted ADPase (and confirmed with CD45) staining detecting that they were as numerous as adult ones. Unexpectedly, most LCs at day 0 expressed CD14 and CD204 while very few were MHCII+ and TLR4+. In contrast, adult LCs lacked all these markers except Langerin, CD205, CD11b, MHCII and TLR4. Intriguingly, the CD204+ and CD14+ LCs predominant at day 0, apparently disappeared by day 4. Upon cutaneous FITC application, LCs were reduced in the skin and a CD204+MHCII+FITC+ population with high levels of CD86 subsequently appeared in DLNs, with a concomitant increased percentage of CD3+CD69+ T cells, strongly suggesting that neonatal LCs were able both to ferry the cutaneous antigen into DLNs and to activate neonatal T cells . Cell cycle analysis indicated that neonatal T cells in DLNs responded with proliferation. Our study reveals that epidermal LCs are present at birth, but their repertoire of endocytic molecules and PRRs differs to that of adult ones. We believe this to be the first description of CDl4, CD204 and TLR4 in neonatal epidermal LCs . Newborns' LCs express molecules to detect antigens during early postnatal periods, are able to take up local antigens and to ferry them into DLNs conveying the information to responsive neonatal T cells.
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http://dx.doi.org/10.3389/fimmu.2020.00744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197463PMC
March 2021

Marine peptides as immunomodulators: -derived synthetic conotoxins induce IL-10 production by regulatory T cells (CD4Foxp3).

Immunopharmacol Immunotoxicol 2019 Aug 24;41(4):463-468. Epub 2019 Jul 24.

Department of Biomedical Innovation, Center for Scientific Research and Higher Education of Ensenada (CICESE) , Baja California , Mexico.

CD4 T lymphocytes are able to differentiate into distinct subtypes according to several immunological scenarios, including T helper (Th)1, Th2, Th17 and regulatory T (Treg) cells. CD4 T cells are phenotypically flexible and have specific ion channels, such as the nicotinic acetylcholine receptors (nAChR) that could be modulated by peptides produced by marine snails, known as conotoxins. Their effect on T lymphocytes has not been explored and emerging evidence suggests that these peptides may have immunomodulatory activities. This study investigated the effect of two -derived synthetic conotoxins on the proliferation and differentiation of T lymphocyte subpopulations Th1, Th2, Th17 and Treg. Cells from lymph nodes of BALB/c mice were cultured in the presence of conotoxins cal14.1b and cal14.2c (5.5 μM), during 96 h. Cell proliferation and intracellular cytokine production (IFN-γ, IL-4, IL-17 and IL-10) were analyzed by flow cytometry. cal14.1b and cal14.2c increased intracellular IL-10 production in Treg (CD3CD4Foxp3) cells and decreased intracellular IL-17 production (CD3CD4) after 72 h of culture. Conotoxins did not show any effect on T cell proliferation nor Th1/Th2 balance. These results suggest that synthetic conotoxins exert immunomodulatory activity, especially by regulating specific functions on T lymphocytes.
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http://dx.doi.org/10.1080/08923973.2019.1641114DOI Listing
August 2019

Dendritic cells and Brucella spp. interaction: the sentinel host and the stealthy pathogen.

Folia Microbiol (Praha) 2020 Feb 19;65(1):1-16. Epub 2019 Feb 19.

Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala S/N, Santo Tomás, 11340, Mexico city, Mexico.

As dendritic cells (DCs) are among the first cells to encounter antigens, these cells trigger both innate and T cell responses, and are the most potent antigen-presenting cells. Brucella spp., which is an intracellular facultative and stealthy pathogen, is able to evade the bactericidal activities of professional phagocytes. Several studies have demonstrated that Brucella can survive and replicate intracellularly, thereby provoking impaired maturation of DCs. Therefore, the interaction between DCs and Brucella becomes an interesting model to study the immune response. In this review, we first will describe the most common techniques for DCs differentiation in vitro as well as general features of brucellosis. Then, the interaction of DCs and Brucella, including pathogen recognition, molecular mechanisms of bacterial pathogenesis, and intracellular trafficking of Brucella to subvert innate response, will be reviewed. Finally, we will debate diversity in immunological DC response and the controversial role of DC activation against Brucella infection.
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http://dx.doi.org/10.1007/s12223-019-00691-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224029PMC
February 2020

Tamoxifen induces toxicity, causes autophagy, and partially reverses dexamethasone resistance in Jurkat T cells.

J Leukoc Biol 2019 05 15;105(5):983-998. Epub 2019 Jan 15.

University Center for Biomedical Research, University of Colima, Colima, Mexico.

Estrogens demonstrate biological activity in numerous organ systems, including the immune system, and exert their effects through estrogen receptors (ER) of two types: intracellular ERα and ERβ that activate transcriptional factors and membrane G protein-coupled ER GPER. The latter is capable to mediate fast activation of cytosolic signaling pathways, influencing transcriptional events in response to estrogens. Tamoxifen (TAM), widely used in chemotherapy of ERα-positive breast cancer, is considered as an ERα antagonist and GPER agonist. TAM was shown to possess "off-target" cytotoxicity, not related to ER in various tumor types. The present work was designed to study biological effects of TAM on the glucocorticoid (GC)-resistant cell line Jurkat, derived from acute lymphoblastic leukemia of T lineage (T-ALL). We have shown that T-ALL cell lines, in contrast to healthy T cells, express only GPER, but not ERα or ERβ. TAM compromised mitochondrial function and reduced the viability and proliferation of Jurkat cells. Additionally, TAM induced autophagy in a GPER-dependent manner. Gene expression profiling revealed the up-regulation of autophagy-related gene ATG5. Interestingly, TAM sensitized Jurkat cells to dexamethasone (DEX) treatment, which may be related to its capacity to cause autophagy. We suggest that TAM-based adjuvant therapy may represent a novel strategy in T-ALL patients handling.
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http://dx.doi.org/10.1002/JLB.2VMA0818-328RDOI Listing
May 2019

The Outer Membrane Vesicles of ATCC 7966: A Proteomic Analysis and Effect on Host Cells.

Front Microbiol 2018 16;9:2765. Epub 2018 Nov 16.

Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico.

Gram-negative bacteria release outer membrane vesicles (OMVs) into the extracellular environment. OMVs have been studied extensively in bacterial pathogens, however, information related with the composition of OMVs is missing. In this study we analyzed the composition of purified OMVs from ATCC 7966 by proteomics. Also we studied the effect of OMVs on human peripheral blood mononuclear cells (PBMCs). Vesicles were grown in agar plates and then purified through ultracentrifugation steps. Purified vesicles showed an average diameter of 90-170 nm. Moreover, 211 unique proteins were found in OMVs from ; some of them are well-known as virulence factors such as: haemolysin Ahh1, RtxA toxin, extracellular lipase, HcpA protein, among others. OMVs from ATCC 7966 induced lymphocyte activation and apoptosis in monocytes, as well as over-expression of pro-inflammatory cytokines. This work contributed to the knowledge of the composition of the vesicles of ATCC 7966 and their interaction with the host cell.
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http://dx.doi.org/10.3389/fmicb.2018.02765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250952PMC
November 2018

Catalase Inhibits the Formation of Mast Cell Extracellular Traps.

Front Immunol 2018 28;9:1161. Epub 2018 May 28.

Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, ENCB-IPN, México City, Mexico.

Tuberculosis is one of the leading causes of human morbidity and mortality. (Mtb) employs different strategies to evade and counterattack immune responses persisting for years. Mast cells are crucial during innate immune responses and help clear infections inflammation or by direct antibacterial activity through extracellular traps (MCETs). Whether Mtb induce MCETs production is unknown. In this study, we report that viable Mtb did not induce DNA release by mast cells, but heat-killed Mtb (HK-Mtb) did. DNA released by mast cells after stimulation with HK-Mtb was complexed with histone and tryptase. MCETs induced with PMA and HK-Mtb were unable to kill live Mtb bacilli. Mast cells stimulated with HK-Mtb induced hydrogen peroxide production, whereas cells stimulated with viable Mtb did not. Moreover, MCETs induction by HK-Mtb was dependent of NADPH oxidase activity, because its blockade resulted in a diminished DNA release by mast cells. Interestingly, catalase-deficient Mtb induced a significant production of hydrogen peroxide and DNA release by mast cells, indicating that catalase produced by Mtb prevents MCETs release by degrading hydrogen peroxide. Our findings show a new strategy employed by Mtb to overcome the immune response through inhibiting MCETs formation, which could be relevant during early stages of infection.
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http://dx.doi.org/10.3389/fimmu.2018.01161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985745PMC
August 2019

(-)-Epicatechin stimulates mitochondrial biogenesis and cell growth in C2C12 myotubes via the G-protein coupled estrogen receptor.

Eur J Pharmacol 2018 Mar 20;822:95-107. Epub 2018 Jan 20.

Departamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Baja California, México. Electronic address:

We have reported on the capacity of (-)-epicatechin ((-)-EPI) to stimulate mitochondrial biogenesis (MiB) in mouse skeletal muscle (SkM). However, the mechanisms mediating the effects of (-)-EPI are not fully understood. We previously identified a role of the G-protein coupled estrogen receptor (GPER) in modulating the vascular effects of (-)-EPI. We therefore tested the hypothesis that GPER mediates (at least in part) the stimulatory effects of (-)-EPI on MiB in SkM cells. As an in vitro model, we employed mouse SkM-derived C2C12 myoblasts differentiated into myotubes. Using confocal microscopy, we detected GPER at the cell surface and cytoplasm in C2C12 myotubes. Treatment with (-)-EPI (3 and 10μM) resulted in the stimulation of MiB as per increases in mitochondrial inner (MitoTracker Red FM fluorescence staining) and outer membrane (porin protein levels) markers, transcription factors involved in MiB stimulation (i.e., nuclear respiratory factor-2 [NRF-2] and mitochondrial transcription factor A [TFAM] protein levels) and citrate synthase (CS) activity levels. (-)-EPI-treated myotubes were longer and wider compared to vehicle-treated myotubes. The effects of (-)-EPI on myotube mitochondria and cell size were larger in magnitude to those observed with the GPER agonist G-1. The chemical blockade and down-regulation (siRNA) of GPER evidenced a partial and complete blockade of measured endpoints following (-)-EPI- or G-1-treatment, respectively. Altogether, results indicate that GPER is expressed in muscle cells and appears to mediate to a significant extent, the stimulatory effects of (-)-EPI on MiB. Thus, GPER activation may account for the stimulatory effects of (-)-EPI on SkM structure/function.
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http://dx.doi.org/10.1016/j.ejphar.2018.01.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809192PMC
March 2018

Corrigendum: Anti-Lipid IgG Antibodies Are Produced Germinal Centers in a Murine Model Resembling Human Lupus.

Front Immunol 2017 12;8:440. Epub 2017 Apr 12.

Department of Cell Biology, Center for Research and Advanced Studies, CINVESTAV-IPN, Instituto Politécnico Nacional (IPN) , Mexico City , Mexico.

[This corrects the article on p. 396 in vol. 7, PMID: 27746783.].
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http://dx.doi.org/10.3389/fimmu.2017.00440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388691PMC
April 2017

A non-hepatotropic parasite infection increases mortality in the acetaminophen-induced acute liver failure murine model: possible roles for IL-5 and IL-6.

Mem Inst Oswaldo Cruz 2016 Dec 31;111(12):757-764. Epub 2016 Oct 31.

Universidad Nacional Autónoma de México, Facultad de Medicina, Unidad de Investigación en Medicina Experimental, Hospital General de México Dr Eduardo Liceaga, Laboratorio de Hígado, Páncreas y Motilidad, Ciudad de México, México.

We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps) on the outcome of acetaminophen-induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group). Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT) levels, CYP2E1 protein, interleukin (IL-) 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group), whereas only one-third of uninfected animals exposed to acetaminophen (APAP group) died. Uninfected (Control group) and infected (Tc group) mice that received the vehicle showed no liver damage. Tc+APAP mice exhibited massive liver necrosis characterised by marked balloning degeneration of hepatocytes and higher serum ALT compared to Control, Tc, and APAP animals. Liver tissue from Tc+APAP mice also displayed increased expression of CYP2E1 protein and higher mRNA and protein levels of IL-5 and IL-6 compared to the other groups. These findings suggest that non-hepatotropic parasite infections may increase mortality following acute liver failure by promoting hepatocyte necrosis via IL-5 and IL-6-dependent CYP2E1 overproduction. This study identifies new potential risk factors associated with severe acute liver failure in patients.
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http://dx.doi.org/10.1590/0074-02760160311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5146742PMC
December 2016

Anti-Lipid IgG Antibodies Are Produced Germinal Centers in a Murine Model Resembling Human Lupus.

Front Immunol 2016 29;7:396. Epub 2016 Sep 29.

Department of Cell Biology, Center for Research and Advanced Studies, CINVESTAV-IPN, National Polytechnic Institute , Mexico City , Mexico.

Anti-lipid IgG antibodies are produced in some mycobacterial infections and in certain autoimmune diseases [such as anti-phospholipid syndrome, systemic lupus erythematosus (SLE)]. However, few studies have addressed the B cell responses underlying the production of these immunoglobulins. Anti-lipid IgG antibodies are consistently found in a murine model resembling human lupus induced by chlorpromazine-stabilized non-bilayer phospholipid arrangements (NPA). NPA are transitory lipid associations found in the membranes of most cells; when NPA are stabilized they can become immunogenic and induce specific IgG antibodies, which appear to be involved in the development of the mouse model of lupus. Of note, anti-NPA antibodies are also detected in patients with SLE and leprosy. We used this model of lupus to investigate the cellular mechanisms that lead to the production of anti-lipid, class-switched IgG antibodies. In this murine lupus model, we found plasma cells (Gr1, CD19, CD138) producing NPA-specific IgGs in the draining lymph nodes, the spleen, and the bone marrow. We also found a significant number of germinal center B cells (IgD, CD19, PNA) specific for NPA in the draining lymph nodes and the spleen, and we identified the presence of NPA in these germinal centers. By contrast, very few NPA-specific, extrafollicular reaction B cells (B220, Blimp1) were found. Moreover, when assessing the anti-NPA IgG antibodies produced during the experimental protocol, we found that the affinity of these antibodies progressively increased over time. Altogether, our data indicate that, in this murine model resembling human lupus, B cells produce anti-NPA IgG antibodies mainly via germinal centers.
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http://dx.doi.org/10.3389/fimmu.2016.00396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040728PMC
September 2016

Listeria monocytogenes induces mast cell extracellular traps.

Immunobiology 2017 02 6;222(2):432-439. Epub 2016 Aug 6.

Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, ENCB-IPN, Mexico; Unidad de Desarrollo e Investigación en Bioprocesos (UDIBI), Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, ENCB-IPN, Mexico. Electronic address:

Mast cells play an essential role in different immunological phenomena including allergy and infectious diseases. Several bacteria induce mast cell activation leading to degranulation and the production of several cytokines and chemokines. However, mast cells also have different microbicidal activities such as phagocytosis and the release of DNA with embedded granular proteins known as Mast Cell Extracellular Traps (MCETs). Although previous reports indicate that extracellular bacteria are able to induce MCETs little is known if intracellular bacteria can induce these structures. In this work, we evaluated MCETs induction by the intracellular bacteria Listeria monocytogenes. We found that mast cells released DNA after stimulation with L. monocytogenes, and this DNA was complexed to histone and tryptase. Before extracellular DNA release, L. monocytogenes induced modifications to the mast cell nuclear envelope and DNA was detected outside the nucleus. L. monocytogenes stimulated mast cells to produce significant amounts of reactive oxygen species (ROS) and blocking NADPH oxidase diminished DNA release by mast cells. Finally, MCETs showed antimicrobial activity against L. monocytogenes that was partially blocked when β-hexosaminidase activity was inhibited. These results show that L. monocytogenes induces mast cells to produce microbicidal MCETs, suggesting a role for mast cells in containing infection beyond the induction of inflammation.
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http://dx.doi.org/10.1016/j.imbio.2016.08.006DOI Listing
February 2017

Germinal center reaction following cutaneous dengue virus infection in immune-competent mice.

Front Immunol 2015 24;6:188. Epub 2015 Apr 24.

Department of Cell Biology, Center for Advanced Research, National Polytechnic Institute, Cinvestav-IPN , Mexico City , Mexico.

Dengue virus (DENV) has four serotypes, which can cause from asymptomatic disease to severe dengue. Heterologous secondary infections have been associated to a greater risk of potentially fatal dengue due to non-neutralizing memory antibodies (Abs), which facilitate the infection, such as anti-precursor membrane (prM) Abs, among other mechanisms. Usually, class-switched memory Abs are generated mainly through germinal centers (GCs). However, the cellular events underlying these Ab responses to DENV, especially during repeated/secondary infections, have been poorly studied. We wanted to know whether there is involvement of GC reactions during cutaneous DENV infection and whether there is any sort of preferential Ab responses to defined viral proteins. Intradermal DENV inoculation at a relatively low dose efficiently infects immune-competent BALB/c mice, inducing higher quantities of DENV-specific GC B cells and larger GCs than the control conditions. Interestingly, GCs exhibited as much prM as envelope (E) and non-structural 3 viral proteins in situ. Intriguingly, despite the much larger abundance of E protein than of prM protein in the virions, infected animals showed similar amounts of circulating Abs and Ag-specific GC B cells both for prM and for E proteins, even significantly higher for prM. To the best of our knowledge, there are no reports of the GC responses during DENV infection. This relatively stronger anti-prM response could be triggered by DENV to preferentially promote Abs against certain viral proteins, which might favor infections by facilitating DENV invasion of host cells. It is thus conceivably that DENV might have evolved to induce this kind of Ab responses.
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http://dx.doi.org/10.3389/fimmu.2015.00188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408864PMC
May 2015

ESAT-6 Targeting to DEC205+ Antigen Presenting Cells Induces Specific-T Cell Responses against ESAT-6 and Reduces Pulmonary Infection with Virulent Mycobacterium tuberculosis.

PLoS One 2015 27;10(4):e0124828. Epub 2015 Apr 27.

Department of Cell Biology, Cinvestav-IPN, Ciudad de México, Mexico.

Airways infection with Mycobacterium tuberculosis (Mtb) is contained mostly by T cell responses, however, Mtb has developed evasion mechanisms which affect antigen presenting cell (APC) maturation/recruitment delaying the onset of Ag-specific T cell responses. Hypothetically, bypassing the natural infection routes by delivering antigens directly to APCs may overcome the pathogen's naturally evolved evasion mechanisms, thus facilitating the induction of protective immune responses. We generated a murine monoclonal fusion antibody (α-DEC-ESAT) to deliver Early Secretory Antigen Target (ESAT)-6 directly to DEC205+ APCs and to assess its in vivo effects on protection associated responses (IFN-γ production, in vivo CTL killing, and pulmonary mycobacterial load). Treatment with α-DEC-ESAT alone induced ESAT-6-specific IFN-γ producing CD4+ T cells and prime-boost immunization prior to Mtb infection resulted in early influx (d14 post-infection) and increased IFN-γ+ production by specific T cells in the lungs, compared to scarce IFN-γ production in control mice. In vivo CTL killing was quantified in relevant tissues upon transferring target cells loaded with mycobacterial antigens. During infection, α-DEC-ESAT-treated mice showed increased target cell killing in the lungs, where histology revealed cellular infiltrate and considerably reduced bacterial burden. Targeting the mycobacterial antigen ESAT-6 to DEC205+ APCs before infection expands specific T cell clones responsible for early T cell responses (IFN-γ production and CTL activity) and substantially reduces lung bacterial burden. Delivering mycobacterial antigens directly to APCs provides a unique approach to study in vivo the role of APCs and specific T cell responses to assess their potential anti-mycobacterial functions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124828PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411092PMC
February 2016

Prolonged exposure to neutrophil extracellular traps can induce mitochondrial damage in macrophages and dendritic cells.

Springerplus 2015 2;4:161. Epub 2015 Apr 2.

Department of Cell Biology, Cinvestav-IPN. AV. IPN No 2508, Zacatenco, C.P. 07330 D.F México.

Neutrophils are one the earliest, crucial innate defenses against innumerable pathogens. Their main microbicidal activities include phagocytosis and degranulation, with many pharmacologically active molecules contributing to inflammation. Recently, a novel antimicrobial mechanism was discovered; the Neutrophil Extracelullar Traps (NETs) formed by extrusion of DNA and associated molecules (histones, elastase, antimicrobial peptides, among others) which trap and kill microorganisms. Since NETs were recently described, research has focused on their induction and microbicidal properties, and recently on disease involvement. However, the functional consequences of NETs interacting with other immune cells, either resident or recruited during early inflammation, have not been assessed. We therefore investigated the consequences of exposing two major APCs, macrophages (Mfs) and conventional Dendritic Cells (cDCs) to NETs. Our data revealed that at early times (30 min), both Antigen Presenting Cells (APCs) showed induction of important costimulatory molecules (CD80, CD86). Unexpectedly, however, at later times (6 and 24 hours) NETs apparently triggered a cell death process in these APCs by a caspase- and Apoptosis induced factor (AIF)-dependent pathway, suggesting mitochondrial damage. By rhodamine-123 labelling we found that in both APCs, relatively prolonged exposure to NETs or their components importantly decreased the mitochondrial membrane potential. Ultrastructural analysis confirmed mitochondrial alterations in both APCs. Our results would suggest that early in inflammation, NETs can activate the two main APCs (Mfs and cDCs), but as the process continues, NETs can then initiate apoptosis of these cells through mitochondrial harm. Conceivable, this "late" induction of cell death in these two APCs might start limiting an ongoing inflammatory process to control it.
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http://dx.doi.org/10.1186/s40064-015-0932-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392041PMC
April 2015