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

我们专注于衔接分子CARD 9的功能，这是通过ITAM偶联受体激活NF-κ B信号通路所必需的，并分析了通过CARD 9通路在IFV感染中激活先天免疫的作用。CARD 9缺陷型小鼠在肺部IFV感染中的存活率比对照小鼠提高。在CARD 9缺陷小鼠中，观察到BAL液中炎性细胞因子的产生和炎性细胞浸润减少，并且肺中病毒RNA的量与对照小鼠相比也略有减少。在CARD 9缺陷小鼠中，IFV刺激的巨噬细胞产生的细胞因子保持不变，但骨髓来源的常规DC或浆细胞样DC产生的细胞因子减少。总的来说，我们的研究结果表明，通过CARD 9途径在DC中激活先天免疫参与了IFV感染肺中的过度炎症。

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.