Journal
MICROBES AND INFECTION
Volume 23, Issue 1, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.micinf.2020.10.001
Keywords
Tuberculosis; EsxA (ESAT-6); Macrophages; Triggering receptor expressed on myeloid cells-1; Innate immunity
Categories
Funding
- Taiwan National Science Council [MOST 104-2314-B-075-027-MY3]
- Taipei Veterans General Hospital [V107C-074, V106C-066]
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The study demonstrates that TREM-1 enhances pro-inflammatory immune responses in mouse macrophages when stimulated with MTB-related proteins, and the gene expression of Trem-1 can be induced by MTB-related stimulation.
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. (C) 2020 Published by Elsevier Masson SAS on behalf of Institut Pasteur.
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