[PDF][PDF] Type I interferon signaling prevents IL-1β-driven lethal systemic hyperinflammation during invasive bacterial infection of soft tissue

V Castiglia, A Piersigilli, F Ebner, M Janos… - Cell host & …, 2016 - cell.com
V Castiglia, A Piersigilli, F Ebner, M Janos, O Goldmann, U Damböck, A Kröger, S Weiss…
Cell host & microbe, 2016cell.com
Summary Type I interferons (IFN-Is) are fundamental for antiviral immunity, but their role in
bacterial infections is contradictory and incompletely described. Streptococcus pyogenes
activates IFN-I production in innate immune cells, and IFN-I receptor 1 (Ifnar1)-deficient mice
are highly susceptible to S. pyogenes infection. Here we report that IFN-I signaling protects
the host against invasive S. pyogenes infection by restricting inflammation-driven damage in
distant tissues. Lethality following infection in Ifnar1-deficient mice is caused by systemically …
Summary
Type I interferons (IFN-Is) are fundamental for antiviral immunity, but their role in bacterial infections is contradictory and incompletely described. Streptococcus pyogenes activates IFN-I production in innate immune cells, and IFN-I receptor 1 (Ifnar1)-deficient mice are highly susceptible to S. pyogenes infection. Here we report that IFN-I signaling protects the host against invasive S. pyogenes infection by restricting inflammation-driven damage in distant tissues. Lethality following infection in Ifnar1-deficient mice is caused by systemically exacerbated levels of the proinflammatory cytokine IL-1β. Critical cellular effectors of IFN-I in vivo are LysM+ and CD11c+ myeloid cells, which exhibit suppression of Il1b transcription upon Ifnar1 engagement. These cells are also the major source of IFN-β, which is significantly induced by S. pyogenes 23S rRNA in an Irf5-dependent manner. Our study establishes IL-1β and IFN-I levels as key homeostatic variables of protective, yet tuned, immune responses against severe invasive bacterial infection.
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