TY - JOUR
T1 - Protection against influenza infection requires early recognition by inflammatory dendritic cells through C-type lectin receptor SIGN-R1
AU - Palomino-Segura, Miguel
AU - Perez, Laurent
AU - Farsakoglu, Yagmur
AU - Virgilio, Tommaso
AU - Latino, Irene
AU - D’Antuono, Rocco
AU - Chatziandreou, Nikolaos
AU - Pizzagalli, Diego U.
AU - Wang, Guojun
AU - García-Sastre, Adolfo
AU - Sallusto, Federica
AU - Carroll, Michael C.
AU - Neyrolles, Olivier
AU - Gonzalez, Santiago F.
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - The early phase of influenza infection occurs in the upper respiratory tract and the trachea, but little is known about the initial events of virus recognition and control of viral dissemination by the immune system. Here, we report that inflammatory dendritic cells (IDCs) are recruited to the trachea shortly after influenza infection through type I interferon-mediated production of the chemokine CCL2. We further show that recruited IDCs express the C-type lectin receptor SIGN-R1, which mediates direct recognition of the virus by interacting with N-linked glycans present in glycoproteins of the virion envelope. Activation of IDCs via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10, which 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, leading to uncontrolled viral proliferation. In sum, our results provide insight into the orchestration of the early cellular and molecular events involved in immune protection against influenza.
AB - The early phase of influenza infection occurs in the upper respiratory tract and the trachea, but little is known about the initial events of virus recognition and control of viral dissemination by the immune system. Here, we report that inflammatory dendritic cells (IDCs) are recruited to the trachea shortly after influenza infection through type I interferon-mediated production of the chemokine CCL2. We further show that recruited IDCs express the C-type lectin receptor SIGN-R1, which mediates direct recognition of the virus by interacting with N-linked glycans present in glycoproteins of the virion envelope. Activation of IDCs via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10, which 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, leading to uncontrolled viral proliferation. In sum, our results provide insight into the orchestration of the early cellular and molecular events involved in immune protection against influenza.
UR - http://www.scopus.com/inward/record.url?scp=85069942762&partnerID=8YFLogxK
U2 - 10.1038/s41564-019-0506-6
DO - 10.1038/s41564-019-0506-6
M3 - Article
C2 - 31358982
AN - SCOPUS:85069942762
SN - 2058-5276
VL - 4
SP - 1930
EP - 1940
JO - Nature Microbiology
JF - Nature Microbiology
IS - 11
ER -