Format

Send to

Choose Destination
Cell Host Microbe. 2016 Mar 9;19(3):375-87. doi: 10.1016/j.chom.2016.02.003.

Type I Interferon Signaling Prevents IL-1β-Driven Lethal Systemic Hyperinflammation during Invasive Bacterial Infection of Soft Tissue.

Author information

1
Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter (VBC), 1030 Vienna, Austria.
2
Institute of Animal Pathology (COMPATH), University of Bern, 3012 Bern, Switzerland; Life Science Faculty, EPFL, 1015 Lausanne, Switzerland.
3
Infection Immunology Research Group, Helmholtz Center for Infection Research, 38124 Braunschweig, Germany.
4
Institute of Medical Microbiology, Otto-von-Guericke-University, 39106 Magdeburg, Germany; Department of Molecular Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
5
Department of Molecular Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
6
Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria; Department of Medicine I, Laboratory of Infection Biology, Medical University of Vienna, 1090 Vienna, Austria.
7
Division of Biology and Medicine, Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.
8
Institute of Medical Microbiology, University of Duisburg-Essen, 45147 Essen, Germany.
9
Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover Medical School and Helmholtz Centre for Infection Research, 30625 Hannover, Germany.
10
Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.
11
Institute of Pharmacology, Medical University of Vienna, 1090 Vienna, Austria; Ludwig Boltzmann Institute for Cancer Research, 1090 Vienna, Austria.
12
Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover Medical School and Helmholtz Centre for Infection Research, 30625 Hannover, Germany; Institute for Laboratory Animal Science, Hannover Medical School, 30625 Hannover, Germany.
13
Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter (VBC), 1030 Vienna, Austria. Electronic address: pavel.kovarik@univie.ac.at.

Abstract

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.

Comment in

PMID:
26962946
DOI:
10.1016/j.chom.2016.02.003
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center