The Role of Fc Gamma Receptors in Broad Protection against Influenza Viruses

Recent studies have revealed multiple roles for Fc gamma receptors (FcγRs) in broad immunity against influenza viruses. Activating FcγR pathways can be harnessed to confer protection mediated by non-neutralizing anti-HA IgGs and to increase the potency of broadly neutralizing anti-HA IgGs and of anti-NA IgGs. Separate FcγR pathways can be targeted to enhance the breadth of antibody responses elicited by seasonal influenza virus vaccines. Here, we review the current understanding of FcγR pathways in broad influenza immunity and suggest mechanisms to bypass FcγR signaling heterogeneity among people that arises from distinctions in structural repertoires of IgG Fc domains.