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Type I IFN Signaling Is Crucial for Host Resistance against Different Species of Pathogenic Bacteria¹

Giuseppe Mancuso^*, Angelina Midiri^*, Carmelo Biondo^*, Concetta Beninati^*, Sebastiana Zummo^*, Roberta Galbo^*, Francesco Tomasello^*, Maria Gambuzza^*, Giancarlo Macrì^*, Alessia Ruggeri^*, Tomas Leanderson and Giuseppe Teti^2,*

^* Dipartimento di Patologia e Microbiologia Sperimentale, Università degli Studi di Messina, Messina, Italy; and Immunology Group, University of Lund, Lund, Sweden

It is known that host cells can produce type I IFNs (IFN-) after exposure to conserved bacterial products, but the functional consequences of such responses on the outcome of bacterial infections are incompletely understood. We show in this study that IFN- signaling is crucial for host defenses against different bacteria, including group B streptococci (GBS), pneumococci, and Escherichia coli. In response to GBS challenge, most mice lacking either the IFN-R or IFN- died from unrestrained bacteremia, whereas all wild-type controls survived. The effect of IFN-R deficiency was marked, with mortality surpassing that seen in IFN-R-deficient mice. Animals lacking both IFN-R and IFN-R displayed additive lethality, suggesting that the two IFN types have complementary and nonredundant roles in host defenses. Increased production of IFN- was detected in macrophages after exposure to GBS. Moreover, in the absence of IFN- signaling, a marked reduction in macrophage production of IFN-, NO, and TNF- was observed after stimulation with live bacteria or with purified LPS. Collectively, our data document a novel, fundamental function of IFN- in boosting macrophage responses and host resistance against bacterial pathogens. These data may be useful to devise alternative strategies to treat bacterial infections.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by a Progetto di Ricerca di Intgresse Nationale grant from Italian Ministry of University and Research of Italy (2004068345_004).

² Address correspondence and reprint requests to Dr. Giuseppe Teti, Dipartimento di Patologia e Microbiologia Sperimentale, Policlinico Universitario, Via Consolare Valeria, 1.98125 Messina, Italy. E-mail address: teti{at}eniware.it

³ Abbreviations used in this paper: IFNAR, IFN- receptor; GBS, group B streptococci; KO, knockout; WT, wild type.

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