Microbiota regulates immune defense against respiratory tract influenza A virus infection
Microbiota regulates immune defense against respiratory tract influenza A virus infection
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DOI：
10.1073/pnas.1019378108
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发表时间：
2011-03-29
影响因子：
11.1
通讯作者：
Iwasaki, Akiko
中科院分区：
文献类型：
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作者：
Ichinohe, Takeshi;Pang, Iris K.;Iwasaki, Akiko
虽然共生菌在维持肠道免疫稳态方面至关重要，但共生菌在其他黏膜表面免疫反应中的作用仍不太清楚。在此，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细胞的产生以及抗体反应具有关键的调节作用。通过使用各种抗生素处理，我们发现新霉素敏感菌与肺部产生有效的免疫反应相关。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。完整的菌群提供信号，导致在稳态下促白细胞介素 - 1β和促白细胞介素 - 18的mRNA表达。在流感病毒感染后，炎症小体激活导致树突状细胞（DCs）从肺部迁移到引流淋巴结并引发T细胞活化。我们的结果揭示了共生菌群通过适当激活炎症小体在调节呼吸道黏膜免疫方面的重要性。
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-1 beta 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.