TY - JOUR
T1 - Alveolar macrophages are critical for broadly-reactive antibody-mediated protection against influenza A virus in mice
AU - He, Wenqian
AU - Chen, Chi Jene
AU - Mullarkey, Caitlin E.
AU - Hamilton, Jennifer R.
AU - Wong, Christine K.
AU - Leon, Paul E.
AU - Uccellini, Melissa B.
AU - Chromikova, Veronika
AU - Henry, Carole
AU - Hoffman, Kevin W.
AU - Lim, Jean K.
AU - Wilson, Patrick C.
AU - Miller, Matthew S.
AU - Krammer, Florian
AU - Palese, Peter
AU - Tan, Gene S.
N1 - Funding Information:
We thank M. Schotsaert for useful discussions, A. Hirsh for protein production, and V. Gillespie for her expertise in scoring the lung sections. We also acknowledge the use of the Mount Sinai Biorepository and Pathology Center of Research Excellence (CORE) and the Flow Cytometry Shared Resource Facility. This work was supported by Center for Research on Influenza Pathogenesis Grant HHSN272201400008C (to P.P. and F.K.) and HHSN272201400005C (to P.C.W.); National Institute of Allergy and Infectious Diseases Grants P01-AI097092 (to P.P., F.K. and P.C.W.), U19-AI109946 (to P.P., F.K. and P.C.W.), and P01-AI097092-04S1 (to P.E.L.); and the Canadian Institutes of Health Research (M.S.M.). The animal studies performed in this study are in accordance with the Institutional Animal Care and Use Committee of the Icahn School of Medicine at Mount Sinai.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - The aim of candidate universal influenza vaccines is to provide broad protection against influenza A and B viruses. Studies have demonstrated that broadly reactive antibodies require Fc-Fc gamma receptor interactions for optimal protection; however, the innate effector cells responsible for mediating this protection remain largely unknown. Here, we examine the roles of alveolar macrophages, natural killer cells, and neutrophils in antibody-mediated protection. We demonstrate that alveolar macrophages play a dominant role in conferring protection provided by both broadly neutralizing and non-neutralizing antibodies in mice. Our data also reveal the potential mechanisms by which alveolar macrophages mediate protection in vivo, namely antibody-induced inflammation and antibody-dependent cellular phagocytosis. This study highlights the importance of innate effector cells in establishing a broad-spectrum antiviral state, as well as providing a better understanding of how multiple arms of the immune system cooperate to achieve an optimal antiviral response following influenza virus infection or immunization.
AB - The aim of candidate universal influenza vaccines is to provide broad protection against influenza A and B viruses. Studies have demonstrated that broadly reactive antibodies require Fc-Fc gamma receptor interactions for optimal protection; however, the innate effector cells responsible for mediating this protection remain largely unknown. Here, we examine the roles of alveolar macrophages, natural killer cells, and neutrophils in antibody-mediated protection. We demonstrate that alveolar macrophages play a dominant role in conferring protection provided by both broadly neutralizing and non-neutralizing antibodies in mice. Our data also reveal the potential mechanisms by which alveolar macrophages mediate protection in vivo, namely antibody-induced inflammation and antibody-dependent cellular phagocytosis. This study highlights the importance of innate effector cells in establishing a broad-spectrum antiviral state, as well as providing a better understanding of how multiple arms of the immune system cooperate to achieve an optimal antiviral response following influenza virus infection or immunization.
UR - http://www.scopus.com/inward/record.url?scp=85031008840&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-00928-3
DO - 10.1038/s41467-017-00928-3
M3 - Article
C2 - 29018261
AN - SCOPUS:85031008840
SN - 2041-1723
VL - 8
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 846
ER -