Intestinal Colonization of IL-2 Deficient Mice with Non-Colitogenic <em>B. vulgatus</em> Prevents DC Maturation and T-Cell Polarization

BackgroundIL-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 FindingsWe 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 (CD40loCD80loMHC-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 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/SignificanceFrom 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-α 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.