Colitogenic and non-colitogenic commensal bacteria differentially trigger DC maturation and Th cell polarization: an important role for IL-6.
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-alpha, 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-alpha 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.
Frick
Julia S
JS
Institute of Medical Microbiology and Hygiene, University of Tübingen, Germany. julia-stefanie.frick@med.uni-tuebingen.de
Zahir
Naima
N
Müller
Martina
M
Kahl
Frauke
F
Bechtold
Oliver
O
Lutz
Manfred B
MB
Kirschning
Carsten J
CJ
Reimann
Jörg
J
Jilge
Burghard
B
Bohn
Erwin
E
Autenrieth
Ingo B
IB
D000818:Animals; D001439:Bacteroides / Q000276:immunology*; D001442:Bacteroides Infections / Q000276:immunology* / Q000382:microbiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D003092:Colitis / Q000276:immunology / Q000382:microbiology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology; D005260:Female; D005434:Flow Cytometry; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12