Suzuki Keiichiro, Meek Bob, Doi Yasuko, Muramatsu Masamichi, Chiba Tsutomu, Honjo Tasuku, Fagarasan Sidonia
Departments of Medical Chemistry and Gastroenterology, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1981-6. doi: 10.1073/pnas.0307317101. Epub 2004 Feb 6.
The mechanism to maintain homeostasis of the gut microbiota remains largely unknown despite its critical role in the body defense. In the intestines of mice with deficiency of activation-induced cytidine deaminase (AID), the absence of hypermutated IgA is partially compensated for by the presence of large amounts of unmutated IgM and normal expression levels of defensins and angiogenins. We show here a predominant and persistent expansion of segmented filamentous bacteria throughout the small intestine of AID(-/-) mice. Reconstitution of lamina propria IgA production in AID(-/-) mice recovered the normal composition of gut flora and abolished the local and systemic activation of the immune system. The results indicate that secretions of IgAs rather than innate defense peptides are critical to regulation of commensal bacterial flora and that the segmented filamentous bacteria antigens are strong stimuli of the mucosal immune system.
尽管肠道微生物群在机体防御中起着关键作用，但其维持自身稳态的机制仍 largely 未知。在激活诱导的胞苷脱氨酶（AID）缺乏的小鼠肠道中，大量未突变的 IgM 的存在以及防御素和血管生成素的正常表达水平部分补偿了高突变 IgA 的缺失。我们在此表明，分段丝状细菌在 AID(-/-)小鼠的整个小肠中占主导地位且持续扩张。在 AID(-/-)小鼠中重建固有层 IgA 的产生恢复了肠道菌群的正常组成，并消除了免疫系统的局部和全身激活。结果表明，IgA 的分泌而非先天防御肽对于共生细菌菌群的调节至关重要，并且分段丝状细菌抗原是粘膜免疫系统的强烈刺激物。
