Alterations in the intestinal microflora have been associated with susceptibility to metabolic and chronic inflammatory diseases or infections in the intestinal microenvironment. In Immunity, Abt et al. show that alterations in the commensal bacteria also lead to defective systemic antiviral immune responses. In several models of non-gastrointestinal viral infection, depletion of the intestinal flora with antibiotics leads to diminished cellular and humoral immune responses, delayed viral clearance and greater pathology. Equal numbers of innate immune cells are recruited to sites of infection, but macrophages from antibiotic-treated mice have lower expression of genes encoding molecules involved in antiviral defense and interferon-responsive pathways, such as Mx1, Stat1, Irf7, Ifit3 and Ifnb at steady state, and show impaired phosphorylation of STAT1 during infection. These results suggest that commensal bacteria maintain the optimal responsiveness of macrophages to stimulation with interferon, which in turn affects the kinetics and amplitude of the immune response. IV

Immunity (14 June 2012) doi:10.1016/j.immuni.2012.04.011