TREM-1 enhances Mycobacterium tuberculosis-induced inflammatory responses in macrophages

Abstract

Triggering receptor expressed on myeloid cells 1 (TREM-1) extensively interacts with toll-like receptors and amplifies pro-inflammatory responses. The effect of TREM-1 on Mycobacterium tuberculosis (MTB)-related immune responses remains to be elucidated. We isolated bone marrow-derived macrophages (BMDMs) from wild-type mice and Trem-1 KO mice and treated them with MTB whole cell lysate and EsxA (ESAT-6). Cytokine production and mRNA expression, including Trem-1, following stimulation were evaluated. Intratracheal instillation of heat-killed MTB (HKMTB) in mice was performed and the presence of TREM-1-positive macrophages was investigated by immunohistochemistry analysis. In our study, BMDMs isolated from wild-type mice produced more pro-inflammatory cytokines and demonstrated higher inflammatory gene expression levels compared with those isolated from Trem-1 KO mice when stimulated with MTB whole cell lysate. EsxA had a synergistic effect with MTB whole cell lysate on the induction of pro-inflammatory responses. The gene expression of Trem-1 was upregulated when treated with MTB-related proteins. TREM-1-positive macrophages were identified in the lung tissues from patients with active TB and from wild-type mice treated with intratracheal instillation of HKMTB. In conclusion, in mouse macrophages, TREM-1 could enhance pro-inflammatory immune responses when stimulated with MTB-related proteins. The gene expression of Trem-1 could also be induced by MTB-related stimulation.

Keywords: EsxA (ESAT-6); Innate immunity; Macrophages; Triggering receptor expressed on myeloid cells-1; Tuberculosis.