MYD88-dependent and -independent activation of TREM-1 via specific TLR ligands

Heng Zheng, Caitlin A. Heiderscheidt, Myung Joo, Xeipei Gao, Nebojsa Knezevic, Dolly Mehta, Ruxana T. Sadikot

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Triggering receptor expressed on myeloid cells (TREM)-1 plays an important role in myeloid cell-activated inflammatory responses. Although TLR ligands such as LPS and lipoteichoic acid have been shown to upregulate TREM-1 expression in macrophage and neutrophils, the role of specific TLR in inducing the expression of TREM-1 remains unclear. In this study, we investigated whether the presence of TLR is necessary for the expression of TREM-1.We show that BM-derived macrophages from TLR4 and TLR2 KO mice failed to induce expression of TREM-1 message and protein in response to their specific ligands. Interestingly, the expression of TREM-1 in response to LPS is not altered in myeloid differentiation factor 88 (MyD88) KO macrophages, suggesting that downstream of TLR a MyD88-independent pathway induces the expression of TREM-1. Inhibiting toll/IL-1R domain-containing adaptor-inducing IFN-β (TRIF) expression by siRNA decreased TREM-1 expression in response to LPS, suggesting that the expression of TREM-1 in response to LPS was mediated by the TRIF signaling pathway. On the other hand, the expression of TREM-1 in response to lipoteichoic acid is dependent on MyD88 expression. These data indicate that the expression of TREM-1 in response to TLR ligands occurs secondary to downstream signaling events and that the presence of TLR is necessary for the expression of TREM-1 in response to their specific ligands. However, the downstream signaling required for the expression of TREM-1 is dependent on the stimulus and the surface receptor through which the signaling is initiated.

Original languageEnglish (US)
Pages (from-to)162-171
Number of pages10
JournalEuropean Journal of Immunology
Volume40
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

Keywords

  • Innate immunity
  • TLR
  • TREM-1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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