Nonredundant roles of TIRAP and MyD88 in airway response to endotoxin, independent of TRIF, IL-1 and IL-18 pathways

Dieudonnée Togbe, Gorse Aurore, Nicolas Noulin, Valérie F J Quesniaux, Silvia Schnyder-Candrian, Bruno Schnyder, Virginie Vasseur, Shizuo Akira, Kasper Hoebe, Bruce Beutler, Bernhard Ryffel, Isabelle Couillin

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Inhaled endotoxins induce an acute inflammatory response in the airways mediated through Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). However, the relative roles of the TLR4 adaptor proteins TIRAP and TRIF and of the MyD88-dependent IL-1 and IL-18 receptor pathways in this response are unclear. Here, we demonstrate that endotoxin-induced acute bronchoconstriction, vascular damage resulting in protein leak, Th1 cytokine and chemokine secretion and neutrophil recruitment in the airways are abrogated in mice deficient for either TIRAP or MyD88, but not in TRIF deficient mice. The contribution of other TLR-independent, MyD88-dependent signaling pathways was investigated in IL-1R1, IL-18R and caspase-1 (ICE)-deficient mice, which displayed normal airway responses to endotoxin. In conclusion, the TLR4-mediated, bronchoconstriction and acute inflammatory lung pathology to inhaled endotoxin critically depend on the expression of both adaptor proteins, TIRAP and MyD88, suggesting cooperative roles, while TRIF, IL-1R1, IL-18R signaling pathways are dispensable.

Original languageEnglish (US)
Pages (from-to)1126-1135
Number of pages10
JournalLaboratory Investigation
Volume86
Issue number11
DOIs
StatePublished - Oct 21 2006

Keywords

  • Airways response
  • Caspase-1
  • Endotoxin
  • Innate immunity
  • TLR signaling

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Togbe, D., Aurore, G., Noulin, N., Quesniaux, V. F. J., Schnyder-Candrian, S., Schnyder, B., Vasseur, V., Akira, S., Hoebe, K., Beutler, B., Ryffel, B., & Couillin, I. (2006). Nonredundant roles of TIRAP and MyD88 in airway response to endotoxin, independent of TRIF, IL-1 and IL-18 pathways. Laboratory Investigation, 86(11), 1126-1135. https://doi.org/10.1038/labinvest.3700473