Detrimental effect of systemic antimicrobial CD4+ T-cell reactivity on gut epithelial integrity.

Kwong Chung, Cheong K C; Ronchi, Francesca; Geuking, Markus (2017). Detrimental effect of systemic antimicrobial CD4+ T-cell reactivity on gut epithelial integrity. Immunology, 150(2), pp. 221-235. Wiley-Blackwell 10.1111/imm.12682

[img]
Preview
Text
Chung_et_al-2017-Immunology.pdf - Published Version
Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND).

Download (834kB) | Preview

Healthy host-microbe mutualism relies on compartmentalization and proper regulation of systemic and mucosal immune responses. Nevertheless, the systemic immune system is frequently exposed to bouts of bacteraemia, which can trigger systemic antimicrobial immune reactivity including CD4+ T cells. Low-level bacteraemia can occur when immune compartmentalization is compromised, for example in the presence of innate immune deficiency or following use of non-steroidal anti-inflammatory drugs. We generated an Escherichia coli strain expressing a defined T helper neo-epitope to study systemic antigen-specific antimicrobial CD4+ T cells and their potential involvement in the pathogenisis of inflammatory bowel diseases. We found that the dose of bacteria required for the induction of systemic antimicrobial CD4+ T-cell proliferation was high and not easily reached under physiological conditions. Importantly, however, when intestinal barrier function was compromised by induced damage to the intestinal epithelium, the presence of systemic antimicrobial CD4+ T cells specific for a single neo-antigen resulted in dramatically increased levels of bacterial translocation. This study therefore demonstrates that systemic antimicrobial CD4+ T-cell reactivity might impact adversely on the mucosa under conditions of reduced barrier function and that despite strong mucosal immune regulation, antigen-specific recognition is still sensitive.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology

UniBE Contributor:

Ronchi, Francesca and Geuking, Markus

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0019-2805

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Thi Thao Anh Pham

Date Deposited:

21 Mar 2018 15:44

Last Modified:

21 Mar 2018 15:44

Publisher DOI:

10.1111/imm.12682

PubMed ID:

27779311

Uncontrolled Keywords:

CD4+ T cells antigen specificity epithelial integrity host-microbe mutualism systemic antimicrobial reactivity

BORIS DOI:

10.7892/boris.110311

URI:

https://boris.unibe.ch/id/eprint/110311

Actions (login required)

Edit item Edit item
Provide Feedback