Journal
CELL HOST & MICROBE
Volume 19, Issue 3, Pages 375-387Publisher
CELL PRESS
DOI: 10.1016/j.chom.2016.02.003
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Funding
- Austrian Science Fund (FWF) [P24540-B21]
- FWF grant [I1621-B22, SFB F28, P25642]
- Paul-Ehrlich-Institute grant
- European Union [PITN-GA-2012-316682]
- Austrian Science Fund (FWF) [P 25642, I 1620, P 24540] Funding Source: researchfish
- Austrian Science Fund (FWF) [P24540, P25642] Funding Source: Austrian Science Fund (FWF)
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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-1 beta. 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-beta, which is significantly induced by S. pyogenes 23S rRNA in an Irf5-dependent manner. Our study establishes IL-1 beta and IFN-I levels as key homeostatic variables of protective, yet tuned, immune responses against severe invasive bacterial infection.
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