Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5354-9. doi: 10.1073/pnas.1019378108. Epub 2011 Mar 14.
Although commensal bacteria are crucial in maintaining immune homeostasis of the intestine, the role of commensal bacteria in immune responses at other mucosal surfaces remains less clear. Here, we show that commensal microbiota composition critically regulates the generation of virus-specific CD4 and CD8 T cells and antibody responses following respiratory influenza virus infection. By using various antibiotic treatments, we found that neomycin-sensitive bacteria are associated with the induction of productive immune responses in the lung. Local or distal injection of Toll-like receptor (TLR) ligands could rescue the immune impairment in the antibiotic-treated mice. Intact microbiota provided signals leading to the expression of mRNA for pro-IL-1β and pro-IL-18 at steady state. Following influenza virus infection, inflammasome activation led to migration of dendritic cells (DCs) from the lung to the draining lymph node and T-cell priming. Our results reveal the importance of commensal microbiota in regulating immunity in the respiratory mucosa through the proper activation of inflammasomes.
尽管共生细菌在维持肠道免疫稳态方面至关重要，但共生细菌在其他黏膜表面的免疫反应中的作用尚不清楚。在这里，我们表明，共生菌群组成对呼吸道流感病毒感染后病毒特异性 CD4 和 CD8 T 细胞和抗体反应的产生具有重要调节作用。通过使用各种抗生素处理，我们发现新霉素敏感细菌与肺部产生有效免疫反应有关。局部或远端注射 Toll 样受体 (TLR) 配体可以挽救抗生素处理小鼠的免疫损伤。完整的微生物群提供信号，导致在稳定状态下表达 pro-IL-1β 和 pro-IL-18 的 mRNA。流感病毒感染后，炎症小体的激活导致树突状细胞 (DC) 从肺部迁移到引流淋巴结并进行 T 细胞启动。我们的结果表明，共生微生物群通过适当激活炎症小体，在调节呼吸道黏膜免疫方面具有重要意义。
