Colitogenic and non-colitogenic commensal bacteria differentiallly trigger DC maturation and Th cell polarization: An important role for IL-6

Abstract

We investigated whether commensal bacteria modulate activation and maturation of bone marrow-derived DC and their ability to prime CD4+ T cells. We used Escherichia coli mpk, which induces colitis in gnotobiotic IL-2-deficient (IL-2-/-) mice, and Bacteroides vulgatus mpk, which prevents E. coli-induced colitis. Stimulation of DC with E. coli induced TNF-α, IL-12 and IL-6 secretion and expression of activation markers. Moreover, stimulation of DC with E. coli increased T cell activation and led to Th1 polarization. Stimulation with B. vulgatus led only to secretion of IL-6, and DC were driven into a semi-mature state with low expression of activation markers and did not promote Th1 responses. B. vulgatus-induced semi-mature DC were non-responsive to stimulation by E. coli in terms of maturation, T cell priming and TNF-α but not IL-6 production. The non-responsiveness of B. vulgatus-stimulated DC was abrogated by addition of anti-IL-6 mAb or mimicked with rIL-6. These data suggest that B. vulgatus-induced IL-6 drives DC into a semi-mature state in which they are non-responsive to proinflammatory activation by E. coli. This in vitro mechanism might contribute to the prevention of E. coli-triggered colitis development by B. vulgatus in vivo; high IL-6 mRNA expression was consistently found in B. vulgatus-colonized or B. vulgatus/E. coli co-colonized IL-2-/- mice and was associated with absence of colitis. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.