Intestinal colonization of IL-2 deficient mice with non-colitogenic B. vulgatus prevents DC maturation and T-cell polarization

Abstract

Background: IL-2 dificient (IL-2-/-) mice mono-colonized with E. coli mpk develop colities whereas IL-2-/- -mice monocolonized with B. vulgatus mpk do not and are even protected from E. coli mpk induced colitis. Methodology/Princial 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 monocolonized with protectrive B, vulgatus mpk or co-colonized wuith E,. coli mpk/B vulgatus mpk featured a semi-mature LP DC phenotype (CD40lo CD80lo MHC-IIhi) 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 exoressiion was more strikingly enhance in mesenteric lymph node D C 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 mopk pronmotes 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 compred to E. coli mpk mono-colonized IL-2-/- -mice. The B. vulgatus mpk mediated suppresion 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 triggeered IL-6 secretion by LP DC in absence oif prinflammatory cytokines such as IL-12 or TN-α induces a semi-marure 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. © 2008 Muller et al.