Publications by authors named "Julia Horstmann"

8 Publications

  • Page 1 of 1

Mucosal-Associated Invariant T (MAIT) Cells Are Highly Activated and Functionally Impaired in COVID-19 Patients.

Viruses 2021 02 3;13(2). Epub 2021 Feb 3.

Department of Internal Medicine II, University Hospital Rechts der Isar, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany.

Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprises mild courses of disease as well as progression to severe disease, characterised by lung and other organ failure. The immune system is considered to play a crucial role for the pathogenesis of COVID-19, although especially the contribution of innate-like T cells remains poorly understood. Here, we analysed the phenotype and function of mucosal-associated invariant T (MAIT) cells, innate-like T cells with potent antimicrobial effector function, in patients with mild and severe COVID-19 by multicolour flow cytometry. Our data indicate that MAIT cells are highly activated in patients with COVID-19, irrespective of the course of disease, and express high levels of proinflammatory cytokines such as IL-17A and TNFα ex vivo. Of note, expression of the activation marker HLA-DR positively correlated with SAPS II score, a measure of disease severity. Upon MAIT cell-specific in vitro stimulation, MAIT cells however failed to upregulate expression of the cytokines IL-17A and TNFα, as well as cytolytic proteins, that is, granzyme B and perforin. Thus, our data point towards an altered cytokine expression profile alongside an impaired antibacterial and antiviral function of MAIT cells in COVID-19 and thereby contribute to the understanding of COVID-19 immunopathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v13020241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913667PMC
February 2021

Methylation of Salmonella Typhimurium flagella promotes bacterial adhesion and host cell invasion.

Nat Commun 2020 04 24;11(1):2013. Epub 2020 Apr 24.

Junior Research Group Infection Biology of Salmonella, Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124, Braunschweig, Germany.

The long external filament of bacterial flagella is composed of several thousand copies of a single protein, flagellin. Here, we explore the role played by lysine methylation of flagellin in Salmonella, which requires the methylase FliB. We show that both flagellins of Salmonella enterica serovar Typhimurium, FliC and FljB, are methylated at surface-exposed lysine residues by FliB. A Salmonella Typhimurium mutant deficient in flagellin methylation is outcompeted for gut colonization in a gastroenteritis mouse model, and methylation of flagellin promotes bacterial invasion of epithelial cells in vitro. Lysine methylation increases the surface hydrophobicity of flagellin, and enhances flagella-dependent adhesion of Salmonella to phosphatidylcholine vesicles and epithelial cells. Therefore, posttranslational methylation of flagellin facilitates adhesion of Salmonella Typhimurium to hydrophobic host cell surfaces, and contributes to efficient gut colonization and host infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-15738-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181671PMC
April 2020

Epidemiologic Risk Factors in a Comparison of a Barrett Esophagus Registry (BarrettNET) and a Case-Control Population in Germany.

Cancer Prev Res (Phila) 2020 04 17;13(4):377-384. Epub 2020 Feb 17.

Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), München, Germany.

Endoscopic screening for Barrett's esophagus as the major precursor lesion for esophageal adenocarcinoma is mostly offered to patients with symptoms of gastroesophageal reflux disease (GERD). However, other epidemiologic risk factors might affect the development of Barrett's esophagus and esophageal adenocarcinoma. Therefore, efforts to improve the efficiency of screening to find the Barrett's esophagus population "at risk" compared with the normal population are needed. In a cross-sectional analysis, we compared 587 patients with Barrett's esophagus from the multicenter German BarrettNET registry to 1976 healthy subjects from the population-based German KORA cohort, with and without GERD symptoms. Data on demographic and lifestyle factors, including age, gender, smoking, alcohol consumption, body mass index, physical activity, and symptoms were collected in a standardized epidemiologic survey. Increased age, male gender, smoking, heavy alcohol consumption, low physical activity, low health status, and GERD symptoms were significantly associated with Barrett's esophagus. Surprisingly, among patients stratified for GERD symptoms, these associations did not change. Demographic, lifestyle, and clinical factors as well as GERD symptoms were associated with Barrett's esophagus development in Germany, suggesting that a combination of risk factors could be useful in developing individualized screening efforts for patients with Barrett's esophagus and GERD in Germany.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1940-6207.CAPR-19-0474DOI Listing
April 2020

BarrettNET-a prospective registry for risk estimation of patients with Barrett's esophagus to progress to adenocarcinoma.

Dis Esophagus 2019 Aug;32(8)

Klinik und Poliklinik für Innere Medizin II, University Hospital rechts der Isar, Technical University of Munich.

Risk stratification in patients with Barrett's esophagus (BE) to prevent the development of esophageal adenocarcinoma (EAC) is an unsolved task. The incidence of EAC and BE is increasing and patients are still at unknown risk. BarrettNET is an ongoing multicenter prospective cohort study initiated to identify and validate molecular and clinical biomarkers that allow a more personalized surveillance strategy for patients with BE. For BarrettNET participants are recruited in 20 study centers throughout Germany, to be followed for progression to dysplasia (low-grade dysplasia or high-grade dysplasia) or EAC for >10 years. The study instruments comprise self-administered epidemiological information (containing data on demographics, lifestyle factors, and health), as well as biological specimens, i.e., blood-based samples, esophageal tissue biopsies, and feces and saliva samples. In follow-up visits according to the individual surveillance plan of the participants, sample collection is repeated. The standardized collection and processing of the specimen guarantee the highest sample quality. Via a mobile accessible database, the documentation of inclusion, epidemiological data, and pathological disease status are recorded subsequently. Currently the BarrettNET registry includes 560 participants (23.1% women and 76.9% men, aged 22-92 years) with a median follow-up of 951 days. Both the design and the size of BarrettNET offer the advantage of answering research questions regarding potential causes of disease progression from BE to EAC. Here all the integrated methods and materials of BarrettNET are presented and reviewed to introduce this valuable German registry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/dote/doz024DOI Listing
August 2019

Molecular Organization of Soluble Type III Secretion System Sorting Platform Complexes.

J Mol Biol 2019 09 6;431(19):3787-3803. Epub 2019 Jul 6.

Center for Structural Systems Biology, Helmholtz Centre for Infection Research, Department of Structural Infection Biology, Notkestraße 85, 22607 Hamburg, Germany; Max Planck Institute for Infection Biology, Structural Systems Biology Group, Charitéplatz 1, 10117 Berlin, Germany; Faculty of Mathematics, Informatics and Natural Sciences, University of Hamburg, Rothenbaumchaussee 19, 20148 Hamburg, Germany. Electronic address:

Many medically relevant Gram-negative bacteria use the type III secretion system (T3SS) to translocate effector proteins into the host for their invasion and intracellular survival. A multi-protein complex located at the cytosolic interface of the T3SS is proposed to act as a sorting platform by selecting and targeting substrates for secretion through the system. However, the precise stoichiometry and 3D organization of the sorting platform components are unknown. Here we reconstitute soluble complexes of the Salmonella Typhimurium sorting platform proteins including the ATPase InvC, the regulator OrgB, the protein SpaO and a recently identified subunit SpaO, which we show to be essential for the solubility of SpaO. We establish domain-domain interactions, determine for the first time the stoichiometry of each subunit within the complexes by native mass spectrometry and gain insight into their organization using small-angle X-ray scattering. Importantly, we find that in solution the assembly of SpaO/SpaO/OrgB/InvC adopts an extended L-shaped conformation resembling the sorting platform pods seen in in situ cryo-electron tomography, proposing that this complex is the core building block that can be conceivably assembled into higher oligomers to form the T3SS sorting platform. The determined molecular arrangements of the soluble complexes of the sorting platform provide important insights into its architecture and assembly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmb.2019.07.004DOI Listing
September 2019

Flagellin phase-dependent swimming on epithelial cell surfaces contributes to productive Salmonella gut colonisation.

Cell Microbiol 2017 08 18;19(8). Epub 2017 Apr 18.

Junior Research Group Infection Biology of Salmonella, Helmholtz Centre for Infection Research, Braunschweig, Germany.

The flagellum is a sophisticated nanomachine and an important virulence factor of many pathogenic bacteria. Flagellar motility enables directed movements towards host cells in a chemotactic process, and near-surface swimming on cell surfaces is crucial for selection of permissive entry sites. The long external flagellar filament is made of tens of thousands subunits of a single protein, flagellin, and many Salmonella serovars alternate expression of antigenically distinct flagellin proteins, FliC and FljB. However, the role of the different flagellin variants during gut colonisation and host cell invasion remains elusive. Here, we demonstrate that flagella made of different flagellin variants display structural differences and affect Salmonella's swimming behaviour on host cell surfaces. We observed a distinct advantage of bacteria expressing FliC-flagella to identify target sites on host cell surfaces and to invade epithelial cells. FliC-expressing bacteria outcompeted FljB-expressing bacteria for intestinal tissue colonisation in the gastroenteritis and typhoid murine infection models. Intracellular survival and responses of the host immune system were not altered. We conclude that structural properties of flagella modulate the swimming behaviour on host cell surfaces, which facilitates the search for invasion sites and might constitute a general mechanism for productive host cell invasion of flagellated bacteria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cmi.12739DOI Listing
August 2017

Complicated grief in patients with unipolar depression.

J Affect Disord 2009 Nov 5;118(1-3):201-4. Epub 2009 Mar 5.

Department of Psychiatry, University of Muenster, Germany.

Background: The loss of a close family member (e.g. child or spouse) has been shown to be one of the most stressful life-events increasing the risk of affective disorders. In the present study, we investigated for the first time the frequency of complicated grief in psychiatric inpatients with unipolar depression. Further, the study was aimed to identify characteristics predicting a complicated grief reaction in depressed patients.

Methods: In a sample of 73 DSM-IV diagnosed unipolar affective disordered inpatients grief, depression, anxiety and psychological stress reaction were assessed.

Results: A high prevalence of loss and impairing complicated grief was found in this sample of unipolar depressed patients. Depressed patients with complicated grief were more severely depressed than depressed patients without complicated grief reactions. Higher traumatic stress and close family membership of the lost person were associated with higher severity of grief.

Conclusions: Comorbid complicated grief appears to contribute to greater severity and poorer functioning in unipolar depressed patients and should be specifically addressed in psychotherapeutic treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2009.01.033DOI Listing
November 2009

Association of MAO-A variant with complicated grief in major depression.

Neuropsychobiology 2007 13;56(4):191-6. Epub 2008 Mar 13.

Department of Psychiatry, University of Munster, Münster, Germany.

Background/aims: It has been suggested that monoamine oxidase A (MAO-A) activity is involved in the pathogenesis of major depression. Bereavement-related complicated grief significantly increases the risk of major depression and has been shown to be influenced by serotonergic tonus, possibly conferred by MAO-A activity. Complicated grief--whose inclusion in DSM-V as a separate mental disorder is under discussion--has been shown to be a distinct syndrome with symptoms not seen in depression. Therefore, in the present study, genetic variation in the MAO-A gene was investigated for its influence on complicated grief in major depression.

Methods: Sixty-six unrelated Caucasian patients (41 female, 25 male) with major depression and a history of bereavement were evaluated for complicated grief using the Inventory of Complicated Grief (ICG), the posttraumatic stress reaction after the loss by means of the Impact of Event Scale (IES-R) and further psychopathological measures. Patients were additionally genotyped for the functional variable number tandem repeat (VNTR) in the promoter region of the MAO-A gene.

Results: The more active longer allele of the MAO-A VNTR was significantly associated with complicated grief in the female subgroup of patients (chi(2) = 9.471, p = 0.002, OR = 9.208, 95% CI 2.129-38.899, Bonferroni-corrected p = 0.012), whereas there was no such effect in male patients. Higher posttraumatic stress reaction was only nominally associated with the more active longer allele of the MAO-A VNTR in the female subgroup of patients (genotypes: chi(2) = 5.939, p = 0.015, OR = 5.333, 95% CI 1.366-20.557, Bonferroni-corrected p = 0.087). No significant associations of MAO-A VNTR with the severity of depressive symptoms (Beck Depression Inventory), anxiety symptoms (Spielberger State-Trait Anxiety Inventory), general mental health (Brief Symptom Inventory), or perceived social support (F-SozU) were found (all p > 0.10).

Conclusion: The present pilot study for the first time suggests a gender-specific contribution of the more active MAO-A VNTR variant to an increased vulnerability for complicated grief as a potential intermediate phenotype of major depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000120624DOI Listing
July 2008
-->