Protection against influenza infection requires early recognition by inflammatory dendritic cells through C-type lectin receptor SIGN-R1

The initial phase of influenza infection occurs in the upper respiratory tract and the trachea. Yet, little is known about the initial events whereby the immune system recognises the virus and controls viral dissemination. Here, we report that inflammatory dendritic cells (IDC) are recruited to the trachea early on following influenza infection through type I interferon-mediated production of the chemokine CCL2. We further show that recruited IDC express the C-type lectin receptor SIGN-R1 that mediates direct recognition of the virus by interacting with the N-linked glycans present in the glycoproteins of the virion envelope. Activation of IDC via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10 that initiate the recruitment of protective natural killer (NK) cells in the infected trachea. In the absence of SIGN-R1, the recruitment and activation of NK cells is impaired, which leads to uncontrolled viral proliferation. Altogether, our results shed light on the orchestration of the early cellular and molecular events involved in the immune protection against influenza.