Tipping the balance in favor of protective immunity during influenza virus infection

Calibrating immune responses to levels that control infection while minimizing damage to host tissues is the primary challenge facing the immune system. Disease manifestations associated with most infections result from host inflammatory responses that, in some cases, are ofsufficient magnitude to result in death. Influenza virus infections occasionally fall into this category. The outcome of human influenza virus infection is heavily influenced by the virulence of the viral strain and the host's immune status. In this issue of PNAS, Aldridge et al. (1) investigate inflammatory responses induced by influenza virus and discover that recruitment of TNF and inducible NOS (iNOS)-producing dendritic cells (TipDCs) correlates with viral strain virulence. Recruitment of TipDCs is substantially greater in mice infected with highly pathogenic influenza virus, and recruitment depends on chemotactic cytokine receptor 2 (CCR2), a chemokine receptor that responds to monocyte chemotactic protein (MCP)-1, MCP-3, and MCP-5. Aldridge et al. demonstrate that CCR2-mediated recruitment of TipDCs enhances viral clearance at later stages of infection by enhancing virus-specific T cell responses.