Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock

Research output: Contribution to journalArticle

Abstract

Toll-like receptor-4 activation by lipopolysaccharide (LPS) induces the expression of interferon-P (IFN-beta) in a MyD88-independent manner. Here we report that mice devoid of the JAK protein tyrosine kinase family member, Tyk2, were resistant to shock induced by high doses of LPS. Basal and LPS-induced expression of IFN-beta and IFN-alpha4 mRNA in Tyk2-null macrophages were diminished. However, Tyk2-null mice showed normal systemic production of nitric oxide and proinflammatory cytokines and the in vivo response to tumor necrosis factor (TNF) was unperturbed. IFN-beta-null but not STAT1-null mice were also resistant to high dose LPS treatment. Together, these data suggest that Tyk2 and IFN-beta are essential effectors in LPS induced lethality.

Details

Authors
  • M Karaghiosoff
  • R Steinborn
  • P Kovarik
  • G Kriegshauser
  • M Baccarini
  • B Donabauer
  • U Reichart
  • T Kolbe
  • C Bogdan
  • Tomas Leanderson
  • D Levy
  • T Decker
  • M Muller
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
Original languageEnglish
Pages (from-to)471-477
JournalNature Immunology
Volume4
Issue number5
Publication statusPublished - 2003
Publication categoryResearch
Peer-reviewedYes