At mucosal surfaces, commensal microbes can promote the development of pathogenic and regulatory adaptive immune cells that help contain pathogens and prevent infection. Whether commensal bacteria can regulate systemic immunity to viruses, however, remains unclear.

Two research groups now report that depletion of the gut microflora impairs the clearance of a viral infection. Andreas Diefenbach and his colleagues (Immunity doi:10.1016/j.immuni.2012.05.020) found that natural killer cell activity was impaired in germ-free mice. These splenic natural killer cells failed to receive priming signals from dendritic cells, which in response to viral infection, normally produce type I interferons (IFN-I). The serum concentrations of IFN-I were reduced in virally infected germ-free mice, and IFN-I injection normalized natural killer cell responses.

David Artis (Immunity doi:10.1016/j.immuni.2012.04.011) and his colleagues report that virus-specific adaptive immune responses are impaired in antibiotic-treated mice. The expression of genes that regulate antiviral immunity was decreased in macrophages isolated from the gut of antibiotic-treated mice. These macrophages responded weakly to IFN stimulation and were impaired in their ability to control viral infection.

Taken together, these studies reveal distinct ways in which commensal bacteria can influence innate immune activation and antiviral immunity.