Type I IFN signaling is crucial for host resistance against different species of pathogenic bacteria.
It is known that host cells can produce type I IFNs (IFN-alphabeta) 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-alphabeta 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-alphabetaR or IFN-beta died from unrestrained bacteremia, whereas all wild-type controls survived. The effect of IFN-alphabetaR deficiency was marked, with mortality surpassing that seen in IFN-gammaR-deficient mice. Animals lacking both IFN-alphabetaR and IFN-gammaR displayed additive lethality, suggesting that the two IFN types have complementary and nonredundant roles in host defenses. Increased production of IFN-alphabeta was detected in macrophages after exposure to GBS. Moreover, in the absence of IFN-alphabeta signaling, a marked reduction in macrophage production of IFN-gamma, NO, and TNF-alpha was observed after stimulation with live bacteria or with purified LPS. Collectively, our data document a novel, fundamental function of IFN-alphabeta in boosting macrophage responses and host resistance against bacterial pathogens. These data may be useful to devise alternative strategies to treat bacterial infections.
Mancuso
Giuseppe
G
Dipartimento di Patologia e Microbiologia Sperimentale, Università degli Studi di Messina, Via Consolare Valeria 1, 98125 Messina, Italy.
Midiri
Angelina
A
Biondo
Carmelo
C
Beninati
Concetta
C
Zummo
Sebastiana
S
Galbo
Roberta
R
Tomasello
Francesco
F
Gambuzza
Maria
M
Macrì
Giancarlo
G
Ruggeri
Alessia
A
Leanderson
Tomas
T
Teti
Giuseppe
G
D000818:Animals; D016470:Bacteremia / Q000235:genetics / Q000276:immunology / Q000628:therapy; D001424:Bacterial Infections / Q000235:genetics / Q000628:therapy; D016898:Interferon-alpha / Q000172:deficiency / Q000276:immunology*; D016899:Interferon-beta / Q000172:deficiency / Q000276:immunology*; D007371:Interferon-gamma / Q000172:deficiency / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000276:immunology; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000276:immunology*; D017471:Receptors, Interferon / Q000172:deficiency / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D000096743:Interferon gamma Receptor
D016898:Interferon-alpha; D016899:Interferon-beta; D007371:Interferon-gamma; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor