Severe influenza is associated with an aberrant inflammatory response that damages lung tissue. A study in Immunity shows that the presence of sialylated IgG — which declines with age — protects against severe influenza. Sialylated IgG binds to the Fc receptor CD209B on alveolar macrophages and induces RE1-silencing transcription factor (REST), which represses NF-κB-driven inflammatory responses and protects against lung tissue damage.

By comparing anti-influenza IgG from patients hospitalized with severe influenza and those with mild disease, the authors found that an abundance of di-galactosylated, sialylated Fc glycoforms predicted a mild disease course. Previous studies suggested that sialylated IgGs have anti-inflammatory properties. The authors therefore tested the effects of purified preparations of sialylated and asialylated human IgGs on influenza virus infection in mice that express human Fcγ receptors. Mice that received sialylated IgG showed delayed weight loss and enhanced survival after an otherwise lethal infection. Interestingly, this protection was not due to an effect on viral load but was associated with fewer lung neutrophils and alveolar macrophages and preserved tissue function (as assessed by blood oxygen levels).