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Intestinal colonization of IL-2 deficient mice with non-colitogenic B. vulgatus prevents DC maturation and T-cell
Martina Müller1, Kerstin Fink, Julia Geisel
1Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany.
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.
Insights
Bacteroides vulgatus, not E. coli, protects against colitis in IL-2 deficient mice by inducing semi-mature dendritic cells. This involves IL-6 secretion, which regulates immune responses in the gut mucosa.
Area of Science:
- Immunology
- Microbiology
- Gastroenterology
Background:
- Interleukin-2 (IL-2) deficient mice develop colitis when colonized with E. coli mpk.
- Colonization with B. vulgatus mpk protects IL-2 deficient mice from E. coli-induced colitis.
Purpose of the Study:
- To investigate how E. coli mpk and B. vulgatus mpk differentially affect intestinal dendritic cells (DCs) in IL-2 deficient mice.
- To understand the role of IL-6 in DC maturation and immune regulation.
Main Methods:
- Mono-colonization and co-colonization of IL-2 deficient mice with E. coli mpk and B. vulgatus mpk.
- Analysis of dendritic cell (DC) phenotype, activation, and maturation in the lamina propria (LP) and mesenteric lymph nodes.
- Measurement of chemokine receptor (CCR7) expression and IL-6 levels (mRNA and protein).
Main Results:
- B. vulgatus mpk induced a semi-mature LP DC phenotype (CD40loCD80loMHC-IIhi), unlike the mature phenotype induced by E. coli mpk.
- B. vulgatus mpk increased IL-6 mRNA and protein expression in LP DCs compared to E. coli mpk.
- IL-6 deficiency in DCs abolished the suppressive effects of B. vulgatus mpk on CCR7 expression and DC migration.
Conclusions:
- B. vulgatus-induced IL-6 secretion by LP DCs promotes a semi-mature phenotype, potentially preventing colitis induction in IL-2 deficient mice.
- IL-6 acts as an immune-regulatory cytokine in the gut mucosa by modulating intestinal DC function.
- Differential modulation of DC maturation by gut bacteria influences the development of colitis.
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