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

W He, CJ Chen, CE Mullarkey, JR Hamilton… - Nature …, 2017 - nature.com
W He, CJ Chen, CE Mullarkey, JR Hamilton, CK Wong, PE Leon, MB Uccellini…
Nature communications, 2017nature.com
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 …
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.
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