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Type I IFN Protects Permissive Macrophages from Legionella pneumophila Infection through an IFN--Independent Pathway¹

Giovanna Schiavoni^*, Claudia Mauri, Davide Carlei^*, Filippo Belardelli^*, Maddalena Castellani Pastoris and Enrico Proietti^2,*

Laboratories of ^* Virology and Bacteriology and Medical Mycology, Istituto Superiore di Sanita’, Rome, Italy; and Center for Rheumatology Research, Department of Medicine, London, United Kingdom

Legionella pneumophila is an intracellular pathogen whose replication in macrophages is mainly controlled by IFN-. 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-) totally inhibits the growth of L. pneumophila in both freshly isolated A/J and in vitro-aged CD1 TG-macrophages. IFN- protective effect on permissive macrophages was comparable to that induced by IFN-. Even low doses of either IFN- or IFN- 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- significantly enhanced their susceptibility to Legionella infection in vitro, thus implying a role of endogenous IFN- in mediating the natural resistance of macrophages to L. pneumophila infection. Finally, addition of anti-IFN--neutralizing Ab did not restore Legionella growth in IFN-- or IFN--treated A/J or CD1 permissive macrophages, indicating that IFN- effect was not mediated by IFN-. This observation was further confirmed by the finding that IFN- was effective in inhibiting L. pneumophila replication in macrophages from IFN- receptor-deficient mice. Taken together, our results provide the first evidence for a role of IFN- 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.

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