Abstract

Triggering receptors expressed on myeloid cells (TREM) are a group of cell surface proteins that contribute to inflammation, allergy, bone homeostasis, neurological development and coagulation, among other cellular processes. Specifically, activation of TREM-1 on monocytes has been shown to enhance the synthesis of multiple proinflammatory cytokines, chemokines and cell surface molecules in the presence of Toll-like receptor (TLR) specific pathogen associated molecular patterns (PAMPs). Presently, little is known about the regulatory role of TLRs on TREM-1 expression and function in macrophages. Accordingly, we examined the expression and function of TREM-1 in bone marrow derived macrophages (BMMØ) from non-sensitized and Aspergillus fumigatus sensitized wild type C57BL/6 (WT) and TLR2 deficient mice (TLR2−/−). In naïve WT BMMØ, TREM-1 expression was upregulated by IFNγ. BMMØ from naïve TLR2−/− mice did not express TREM-1 transcripts nor was it altered by cytokine or PAMP activation. In the context of sensitization, WT BMMØ expressed greater TREM-1 levels when compared with naive WT BMMØ. TREM-1 was detected in sensitized TLR2 −/− BMMØ but at much lower levels than sensitized WT BMMØ. Finally, both IFNγ and IL-13 increased expression of TREM-1 sensitized WT and TLR2−/− BMMØ. Thus, TLR2 expression was required for TREM-1 expression by BMMØ. Also, TREM-1 expression is markedly increased in BMMØ derived from allergic mice confirming a role for this receptor in allergic responses. Thus, regulation of TREM-1 expression may be a therapeutic target in allergic airway disease.

HL069865

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