Frick Julia S, Zahir Naima, Müller Martina, Kahl Frauke, Bechtold Oliver, Lutz Manfred B, Kirschning Carsten J, Reimann Jörg, Jilge Burghard, Bohn Erwin, Autenrieth Ingo B
Institute of Medical Microbiology and Hygiene, University of Tübingen, Germany.
Eur J Immunol. 2006 Jun;36(6):1537-47. doi: 10.1002/eji.200635840.
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.
我们研究了共生细菌是否调节骨髓来源的树突状细胞（DC）的激活和成熟及其启动CD4(+) T细胞的能力。我们使用了可在无菌白细胞介素-2缺陷（IL-2(-/-)）小鼠中诱发结肠炎的大肠杆菌mpk，以及可预防大肠杆菌诱发结肠炎的普通拟杆菌mpk。用大肠杆菌刺激DC可诱导肿瘤坏死因子-α（TNF-α）、白细胞介素-12（IL-12）和白细胞介素-6（IL-6）的分泌以及激活标志物的表达。此外，用大肠杆菌刺激DC可增加T细胞激活并导致Th1极化。用普通拟杆菌刺激仅导致IL-6分泌，DC被驱动进入激活标志物低表达的半成熟状态，且不促进Th1反应。普通拟杆菌诱导的半成熟DC在成熟、T细胞启动和TNF-α分泌方面对大肠杆菌刺激无反应，但IL-6产生不受影响。添加抗IL-6单克隆抗体可消除普通拟杆菌刺激的DC的无反应性，或用重组IL-6模拟该现象。这些数据表明，普通拟杆菌诱导的IL-6将DC驱动到半成熟状态，在此状态下它们对大肠杆菌的促炎激活无反应。这种体外机制可能有助于普通拟杆菌在体内预防大肠杆菌引发的结肠炎发展；在普通拟杆菌定殖或普通拟杆菌/大肠杆菌共定殖的IL-2(-/-)小鼠中始终发现高IL-6 mRNA表达，且与无结肠炎相关。
