Elucidation of innate immune responses through ITAM coupled receptor-CARD9 signaling in influenza virus infection.

我们重点研究了适配分子CARD9的功能，它是通过ITAM偶联受体激活NF-kB信号通路所必需的，并分析了CARD9途径在IFV感染中对天然免疫激活的作用。在肺部IFV感染中，CARD9缺陷小鼠的存活率比对照小鼠有所提高。CARD9基因缺陷小鼠BAL液中炎性细胞因子的产生减少，炎性细胞浸润减少，肺组织中病毒RNA含量也略有下降。在CARD9缺陷小鼠中，IFV刺激的巨噬细胞产生的细胞因子没有变化，但骨髓来源的常规树突状细胞或浆细胞样树突状细胞产生的细胞因子减少。综上所述，我们的研究结果表明，通过CARD9途径激活的树突状细胞的天然免疫参与了IFV感染肺的过度炎症。

We focused on the function of the adaptor molecule CARD9, which is essential for NF-kB signaling pathway activation through ITAM-coupled receptors, and analyzed the role for innate immune activation through the CARD9 pathway in IFV infection. CARD9-deficient mice showed improved survival rate compared with control mice in pulmonary IFV infection. In CARD9-deficient mice, decrease in the production of inflammatory cytokines in BAL fluid and the inflammatory cell infiltration was observed, and the amount of viral RNA in the lungs was also slightly decreased compared with control mice. Cytokine production by macrophages stimulated with IFV remained unchanged, but that by bone marrow-derived conventional DCs or plasmacytoid DCs was decreased in CARD9-deficient mice. Collectively, our findings indicate that activation of innate immunity through the CARD9 pathway in DCs is involved in the excessive inflammation in IFV-infected lungs.