Regulatory T cells promote a protective Th17-associated immune response to intestinal bacterial infection with C. rodentium.

2.50
Hdl Handle:
http://hdl.handle.net/10033/338859
Title:
Regulatory T cells promote a protective Th17-associated immune response to intestinal bacterial infection with C. rodentium.
Authors:
Wang, Z; Friedrich, C; Hagemann, S C; Korte, W H; Goharani, N; Cording, S; Eberl, G; Sparwasser, T ( 0000-0001-5645-902X ) ; Lochner, M
Abstract:
Intestinal infection with the mouse pathogen Citrobacter rodentium induces a strong local Th17 response in the colon. Although this inflammatory immune response helps to clear the pathogen, it also induces inflammation-associated pathology in the gut and thus, has to be tightly controlled. In this project, we therefore studied the impact of Foxp3(+) regulatory T cells (Treg) on the infectious and inflammatory processes elicited by the bacterial pathogen C. rodentium. Surprisingly, we found that depletion of Treg by diphtheria toxin in the Foxp3(DTR) (DEREG) mouse model resulted in impaired bacterial clearance in the colon, exacerbated body weight loss, and increased systemic dissemination of bacteria. Consistent with the enhanced susceptibility to infection, we found that the colonic Th17-associated T-cell response was impaired in Treg-depleted mice, suggesting that the presence of Treg is crucial for the establishment of a functional Th17 response after the infection in the gut. As a consequence of the impaired Th17 response, we also observed less inflammation-associated pathology in the colons of Treg-depleted mice. Interestingly, anti-interleukin (IL)-2 treatment of infected Treg-depleted mice restored Th17 induction, indicating that Treg support the induction of a protective Th17 response during intestinal bacterial infection by consumption of local IL-2.
Affiliation:
Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research,Feodor-Lyner-Str. 7, 30625 Hannover, Germany.
Citation:
Regulatory T cells promote a protective Th17-associated immune response to intestinal bacterial infection with C. rodentium. 2014, 7 (6):1290-301 Mucosal Immunol
Journal:
Mucosal immunology
Issue Date:
Nov-2014
URI:
http://hdl.handle.net/10033/338859
DOI:
10.1038/mi.2014.17
PubMed ID:
24646939
Type:
Article
Language:
en
ISSN:
1935-3456
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorWang, Zen
dc.contributor.authorFriedrich, Cen
dc.contributor.authorHagemann, S Cen
dc.contributor.authorKorte, W Hen
dc.contributor.authorGoharani, Nen
dc.contributor.authorCording, Sen
dc.contributor.authorEberl, Gen
dc.contributor.authorSparwasser, Ten
dc.contributor.authorLochner, Men
dc.date.accessioned2015-01-26T11:47:37Zen
dc.date.available2015-01-26T11:47:37Zen
dc.date.issued2014-11en
dc.identifier.citationRegulatory T cells promote a protective Th17-associated immune response to intestinal bacterial infection with C. rodentium. 2014, 7 (6):1290-301 Mucosal Immunolen
dc.identifier.issn1935-3456en
dc.identifier.pmid24646939en
dc.identifier.doi10.1038/mi.2014.17en
dc.identifier.urihttp://hdl.handle.net/10033/338859en
dc.description.abstractIntestinal infection with the mouse pathogen Citrobacter rodentium induces a strong local Th17 response in the colon. Although this inflammatory immune response helps to clear the pathogen, it also induces inflammation-associated pathology in the gut and thus, has to be tightly controlled. In this project, we therefore studied the impact of Foxp3(+) regulatory T cells (Treg) on the infectious and inflammatory processes elicited by the bacterial pathogen C. rodentium. Surprisingly, we found that depletion of Treg by diphtheria toxin in the Foxp3(DTR) (DEREG) mouse model resulted in impaired bacterial clearance in the colon, exacerbated body weight loss, and increased systemic dissemination of bacteria. Consistent with the enhanced susceptibility to infection, we found that the colonic Th17-associated T-cell response was impaired in Treg-depleted mice, suggesting that the presence of Treg is crucial for the establishment of a functional Th17 response after the infection in the gut. As a consequence of the impaired Th17 response, we also observed less inflammation-associated pathology in the colons of Treg-depleted mice. Interestingly, anti-interleukin (IL)-2 treatment of infected Treg-depleted mice restored Th17 induction, indicating that Treg support the induction of a protective Th17 response during intestinal bacterial infection by consumption of local IL-2.en
dc.language.isoenen
dc.titleRegulatory T cells promote a protective Th17-associated immune response to intestinal bacterial infection with C. rodentium.en
dc.typeArticleen
dc.contributor.departmentInstitute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research,Feodor-Lyner-Str. 7, 30625 Hannover, Germany.en
dc.identifier.journalMucosal immunologyen

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