Fc Receptor-Mediated Phagocytosis Makes a Significant Contribution to Clearance of Influenza Virus Infections

Abstract

Fc receptors for IgG expressed on macrophages and NK cells are important mediators of opsonophagocytosis and Ab-dependent cell-mediated cytotoxicity. Phagocyte-mediated opsonophagocytosis is pivotal for protection against bacteria, but its importance in recovery from infection with intracellular pathogens is unclear. We have now investigated the role of opsonophagocytosis in protection against lethal influenza virus infection by using FcR γ−/− mice. Absence of the FcR γ-chain did not affect the expression of IFN-γ 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 γ−/− mice were similar to levels seen in FcR γ+/+ mice. Nevertheless, FcR γ−/− mice were highly susceptible to influenza infection, even in the presence of anti-influenza Abs from immune FcR γ+/+ mice. NK cells were not necessary for the observed Ab-mediated viral clearance, but macrophages were found to be capable of actively ingesting opsonized virus particles. We conclude that Fc receptor-mediated phagocytosis plays a pivotal role in clearance of respiratory virus infections.

Fcγ Receptors Regulate Immune Activation and Susceptibility during Mycobacterium tuberculosis Infection

“…Deficiency of the Fc␥-chain was previously reported to affect the progression of infection with other intracellular pathogens, including influenza and Leishmania species (17)(18)(19)(20)(21)(22). Diminished survival was associated with statistically significantly elevated bacterial burden in the lungs and spleens 15 wk, but not 3 wk, after infection.…”

“…Other reports have previously implicated Fc␥R as affecting host defense in infectious disease models (17)(18)(19)(20)(21)(22)47). Interestingly, lupus-associated polymorphisms in Fc␥RIIB have been correlated with reduced susceptibility to malaria in humans (21), suggesting that infectious diseases may provide selective pressure for autoimmunity.…”

“…Separated into activating and inhibiting types, Fc␥R mediate immune activation or suppression based upon a threshold determined by the summation of their reciprocal signals (16). Murine models of Fc␥R deficiency have been useful in assessing the relevance of these receptors against intracellular pathogens, including Chlamydia trachomatis, influenza virus, Leishmania species, Plasmodium, and Salmonella enterica (17)(18)(19)(20)(21)(22). However, no such study had yet been conducted with M. tuberculosis, possibly because of the prevailing view that humoral immunity has little or no role in host defense against this pathogen.…”

Fc functional antibodies in humans with severe H7N9 and seasonal influenza

“…The narrow specificity of influenza NAbs, particularly those directed against the immunodominant hemagglutinin (HA) head, is problematic for protection against influenza viruses (14,15). However, in addition to neutralization, Abs can also mediate several functions through their Fc region, including complement-dependent cytotoxicity (CDC) (16,17), Ab-dependent cellular cytotoxicity (ADCC) (18)(19)(20)(21), and Ab-dependent phagocytosis (ADP) (22). ADCC occurs when Abs bind to viral antigens on infected cells and engage receptors for the Fc region of IgG (FcγRs) found on the surface of innate immune effector cells.…”

Universal vaccine against influenza virus: Linking TLR signaling to anti‐viral protection

“…However, M2e is poorly expressed on the viral particle [23] and M2e-specific antibodies fail to neutralize the virus during natural infection. Indeed, protection is dependent on Fcγ-receptor expression on macrophages [24,25] and/or NK cells [17].…”