title: Type I IFN protects permissive macrophages from Legionella pneumophila infection through an IFN-gamma-independent pathway.
abstract: Legionella pneumophila is an intracellular pathogen whose replication in macrophages is mainly controlled by IFN-gamma. Freshly isolated peritoneal macrophages elicited in vivo with thioglycolate (TG) from A/J mice are highly permissive to L. pneumophila growth in vitro, while TG-elicited macrophages from CD1 mice are resistant. In this study, we show that when CD1 TG-macrophages are cultured for 7 days, they become permissive to Legionella infection. We demonstrate that treatment with type I IFN (IFN-alphabeta) totally inhibits the growth of L. pneumophila in both freshly isolated A/J and in vitro-aged CD1 TG-macrophages. IFN-alphabeta protective effect on permissive macrophages was comparable to that induced by IFN-gamma. Even low doses of either IFN-alpha or IFN-beta alone were effective in inhibiting L. pneumophila multiplication in macrophage cultures. Notably, treatment of resistant, freshly isolated CD1 TG-macrophages with Ab to mouse IFN-alphabeta significantly enhanced their susceptibility to Legionella infection in vitro, thus implying a role of endogenous IFN-alphabeta in mediating the natural resistance of macrophages to L. pneumophila infection. Finally, addition of anti-IFN-gamma-neutralizing Ab did not restore Legionella growth in IFN-alpha- or IFN-beta-treated A/J or CD1 permissive macrophages, indicating that IFN-alphabeta effect was not mediated by IFN-gamma. This observation was further confirmed by the finding that IFN-alphabeta was effective in inhibiting L. pneumophila replication in macrophages from IFN-gamma receptor-deficient mice. Taken together, our results provide the first evidence for a role of IFN-alphabeta in the control of L. pneumophila infection in mouse models of susceptible macrophages and suggest the existence of different pathways for the control of intracellular bacteria in macrophages.
authors.affiliation: Laboratory of Virology, Istituto Superiore di Sanita', Rome, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Schiavoni
authors.forename: Claudia
authors.initials: C
authors.lastname: Mauri
authors.forename: Davide
authors.initials: D
authors.lastname: Carlei
authors.forename: Filippo
authors.initials: F
authors.lastname: Belardelli
authors.forename: Maddalena Castellani
authors.initials: MC
authors.lastname: Pastoris
authors.forename: Enrico
authors.initials: E
authors.lastname: Proietti
mesh_terms: D000818:Animals; D007370:Interferon Type I / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016952:Legionella pneumophila / Q000276:immunology; D007877:Legionnaires' Disease / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice
chemical_list: D007370:Interferon Type I; D007371:Interferon-gamma