Intestinal colonization of IL-2 deficient mice with non-colitogenic B. vulgatus prevents DC maturation and T-cell polarization.
BACKGROUND: IL-2 deficient (IL-2(-/-)) mice mono-colonized with E. coli mpk develop colitis whereas IL-2(-/-)-mice mono-colonized with B. vulgatus mpk do not and are even protected from E. coli mpk induced colitis. METHODOLOGY/PRINCIPAL FINDINGS: We investigated if mono-colonization with E. coli mpk...
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doaj-83a33e8e12f642f8b622a25ef7100c0c2020-11-25T02:21:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-0136e237610.1371/journal.pone.0002376Intestinal colonization of IL-2 deficient mice with non-colitogenic B. vulgatus prevents DC maturation and T-cell polarization.Martina MüllerKerstin FinkJulia GeiselFrauke KahlBurghardt JilgeJörg ReimannNicolas MachIngo B AutenriethJulia S FrickBACKGROUND: IL-2 deficient (IL-2(-/-)) mice mono-colonized with E. coli mpk develop colitis whereas IL-2(-/-)-mice mono-colonized with B. vulgatus mpk do not and are even protected from E. coli mpk induced colitis. METHODOLOGY/PRINCIPAL FINDINGS: We investigated if mono-colonization with E. coli mpk or B. vulgatus mpk differentially modulates distribution, activation and maturation of intestinal lamina propria (LP) dendritic cells (DC). LP DC in mice mono-colonized with protective B. vulgatus mpk or co-colonized with E. coli mpk/B. vulgatus mpk featured a semi-mature LP DC phenotype (CD40(lo)CD80(lo)MHC-II(hi)) whereas mono-colonization with colitogenic E. coli mpk induced LP DC activation and maturation prior to onset of colitis. Accordingly, chemokine receptor (CCR) 7 surface expression was more strikingly enhanced in mesenteric lymph node DC from E. coli mpk than B. vulgatus mpk mono- or co-colonized mice. Mature but not semi-mature LP DC promoted Th1 polarization. As B. vulgatus mpk promotes differentiation of semi-mature DC presumably by IL-6, mRNA and protein expression of IL-6 was investigated in LP DC. The data demonstrated that IL-6 mRNA and protein was increased in LP DC of B. vulgatus mpk as compared to E. coli mpk mono-colonized IL-2(-/-)-mice. The B. vulgatus mpk mediated suppression of CCR7 expression and DC migration was abolished in IL-6(-/-)-DC in vitro. CONCLUSIONS/SIGNIFICANCE: From this data we conclude that the B. vulgatus triggered IL-6 secretion by LP DC in absence of proinflammatory cytokines such as IL-12 or TNF-alpha induces a semi-mature LP DC phenotype, which might prevent T-cell activation and thereby the induction of colitis in IL-2(-/-)-mice. The data provide new evidence that IL-6 might act as an immune regulatory cytokine in the mucosa by targeting intestinal DC.http://europepmc.org/articles/PMC2398772?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Martina Müller Kerstin Fink Julia Geisel Frauke Kahl Burghardt Jilge Jörg Reimann Nicolas Mach Ingo B Autenrieth Julia S Frick |
spellingShingle |
Martina Müller Kerstin Fink Julia Geisel Frauke Kahl Burghardt Jilge Jörg Reimann Nicolas Mach Ingo B Autenrieth Julia S Frick Intestinal colonization of IL-2 deficient mice with non-colitogenic B. vulgatus prevents DC maturation and T-cell polarization. PLoS ONE |
author_facet |
Martina Müller Kerstin Fink Julia Geisel Frauke Kahl Burghardt Jilge Jörg Reimann Nicolas Mach Ingo B Autenrieth Julia S Frick |
author_sort |
Martina Müller |
title |
Intestinal colonization of IL-2 deficient mice with non-colitogenic B. vulgatus prevents DC maturation and T-cell polarization. |
title_short |
Intestinal colonization of IL-2 deficient mice with non-colitogenic B. vulgatus prevents DC maturation and T-cell polarization. |
title_full |
Intestinal colonization of IL-2 deficient mice with non-colitogenic B. vulgatus prevents DC maturation and T-cell polarization. |
title_fullStr |
Intestinal colonization of IL-2 deficient mice with non-colitogenic B. vulgatus prevents DC maturation and T-cell polarization. |
title_full_unstemmed |
Intestinal colonization of IL-2 deficient mice with non-colitogenic B. vulgatus prevents DC maturation and T-cell polarization. |
title_sort |
intestinal colonization of il-2 deficient mice with non-colitogenic b. vulgatus prevents dc maturation and t-cell polarization. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2008-01-01 |
description |
BACKGROUND: IL-2 deficient (IL-2(-/-)) mice mono-colonized with E. coli mpk develop colitis whereas IL-2(-/-)-mice mono-colonized with B. vulgatus mpk do not and are even protected from E. coli mpk induced colitis. METHODOLOGY/PRINCIPAL FINDINGS: We investigated if mono-colonization with E. coli mpk or B. vulgatus mpk differentially modulates distribution, activation and maturation of intestinal lamina propria (LP) dendritic cells (DC). LP DC in mice mono-colonized with protective B. vulgatus mpk or co-colonized with E. coli mpk/B. vulgatus mpk featured a semi-mature LP DC phenotype (CD40(lo)CD80(lo)MHC-II(hi)) whereas mono-colonization with colitogenic E. coli mpk induced LP DC activation and maturation prior to onset of colitis. Accordingly, chemokine receptor (CCR) 7 surface expression was more strikingly enhanced in mesenteric lymph node DC from E. coli mpk than B. vulgatus mpk mono- or co-colonized mice. Mature but not semi-mature LP DC promoted Th1 polarization. As B. vulgatus mpk promotes differentiation of semi-mature DC presumably by IL-6, mRNA and protein expression of IL-6 was investigated in LP DC. The data demonstrated that IL-6 mRNA and protein was increased in LP DC of B. vulgatus mpk as compared to E. coli mpk mono-colonized IL-2(-/-)-mice. The B. vulgatus mpk mediated suppression of CCR7 expression and DC migration was abolished in IL-6(-/-)-DC in vitro. CONCLUSIONS/SIGNIFICANCE: From this data we conclude that the B. vulgatus triggered IL-6 secretion by LP DC in absence of proinflammatory cytokines such as IL-12 or TNF-alpha induces a semi-mature LP DC phenotype, which might prevent T-cell activation and thereby the induction of colitis in IL-2(-/-)-mice. The data provide new evidence that IL-6 might act as an immune regulatory cytokine in the mucosa by targeting intestinal DC. |
url |
http://europepmc.org/articles/PMC2398772?pdf=render |
work_keys_str_mv |
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