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- Title
Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock.
- Authors
Karaghiosoff, Marina; Steinborn, Ralf; Kovarik, Pavel; Kriegshäuser, Gernot; Baccarini, Manuela; Donabauer, Birgit; Reichart, Ursula; Kolbe, Thomas; Bogdan, Christian; Leanderson, Tomas; Levy, David; Decker, Thomas; Müller, Mathias
- Abstract
Toll-like receptor-4 activation by lipopolysaccharide (LPS) induces the expression of interferon-beta (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.
- Publication
Nature immunology, 2003, Vol 4, Issue 5, p471
- ISSN
1529-2908
- Publication type
Journal Article
- DOI
10.1038/ni910