Interferons Direct an Effective Innate Response to

Legionella pneumophila remains an important opportunistic pathogen of human macrophages. Its more limited ability to replicate in murine macrophages has been attributed to redun-dant innate sensor systems that detect and effectively respond to this infection. The current studies evaluate the role of one of these innate response systems, the type I interferon (IFN-I) autocrine loop. The ability of L. pneumophila to induce IFN-I expression was found to be dependent on IRF-3, but not NF-B. Secreted IFN-Is then in turn suppress the intracellular replica-tion of L. pneumophila. Surprisingly, this suppression is medi-ated by a pathway that is independent of Stat1, Stat2, Stat3, but correlates with the polarization of macrophages toward the M1 or classically activated phenotype. Legionella pneumophila, the causative agent of Legionnaires’ Disease, remains an important cause of human morbidity (1)