Alveolar macrophages are critical for broadly-reactive antibody-mediated protection against influenza A virus in mice

Wenqian He, Chi-Jene Chen, Caitlin E. Mullarkey, Jennifer R. Hamilton, Christine K. Wong, Paul E. Leon, Melissa B. Uccellini, Veronika Chromikova, Carole Henry, Kevin W. Hoffman, Jean K. Lim, Patrick C. Wilson, Matthew S. Miller, Florian Krammer, Peter Palese and Gene S. Tan ()
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Wenqian He: Icahn School of Medicine at Mount Sinai
Chi-Jene Chen: Icahn School of Medicine at Mount Sinai
Caitlin E. Mullarkey: Icahn School of Medicine at Mount Sinai
Jennifer R. Hamilton: Icahn School of Medicine at Mount Sinai
Christine K. Wong: Icahn School of Medicine at Mount Sinai
Paul E. Leon: Icahn School of Medicine at Mount Sinai
Melissa B. Uccellini: Icahn School of Medicine at Mount Sinai
Veronika Chromikova: Icahn School of Medicine at Mount Sinai
Carole Henry: The University of Chicago
Kevin W. Hoffman: Icahn School of Medicine at Mount Sinai
Jean K. Lim: Icahn School of Medicine at Mount Sinai
Patrick C. Wilson: The University of Chicago
Matthew S. Miller: McMaster University
Florian Krammer: Icahn School of Medicine at Mount Sinai
Peter Palese: Icahn School of Medicine at Mount Sinai
Gene S. Tan: Icahn School of Medicine at Mount Sinai

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-00928-3

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