Fc receptor-mediated phagocytosis makes a significant contribution to clearance of influenza virus infections

Fc receptors for IgG expressed on macrophages and NK cells are important me diators of opsonophagocytosis and Ab-dependent cell-mediated cytotoxicity. Phagocyte-mediated opsonophagocytosis is pivotal for protection against bac teria, but its importance in recovery from infection with intracellular pat hogens is unclear. We have now investigated the role of opsonophagocytosis in protection against lethal influenza virus infection by using FcR gamma ( -/-) mice. Absence of the FcR gamma -chain did not affect the expression of IFN-gamma and IL-10 in the lungs and spleens after intranasal immunization with an influenza subunit vaccine. Titers of serum and respiratory Abs of the IgM, IgG1, IgG2a, and IgA isotypes in FcR gamma (-/-) mice were similar to levels seen in FcR gamma (+/+) mice. Nevertheless, FcR y(-/-) mice were highly susceptible to influenza infection, even in the presence of anti-in fluenza Abs from immune FcR gamma (+/+) mice. NK cells were not necessary f or the observed Ab-mediated viral clearance, but macrophages were found to be capable of actively ingesting opsonized virus particles. We conclude tha t Fc receptor-mediated phagocytosis plays a pivotal role in clearance of re spiratory virus infections.