Role of TREM-1 in pulmonary tuberculosis patients- analysis of serum soluble TREM-1 levels

Jia-Yih Feng,Yung-Yang Lin,Yi-Chen Yeh,Sheng-Wei Pan,Nien-Jung Chen,Wei-Juin Su

doi:10.1038/s41598-018-26478-2

Abstract

Triggering receptor expressed on myeloid cells 1 (TREM-1) amplifies inflammatory responses and is upregulated during sepsis and pulmonary infection. The association between serum soluble TREM-1 (sTREM-1) level and pulmonary tuberculosis (PTB) disease deserves investigation. In the present study, patients with PTB, latent TB infection (LTBI), and non-TB, non-LTBI subjects were prospectively enrolled and serum levels of sTREM-1, sTREM-2, and C-reactive protein (CRP) were measured. We correlated serum biomarkers and clinical presentations and treatment outcomes of PTB cases. We also utilized immunohistochemistry (IHC) to visualize TREM-1-expressing cells in lung tissues from PTB patients. A total of 86 PTB, 41 LTBI, and 20 non-TB, non-LTBI subjects were enrolled. Serum levels of sTREM-1 and CRP significantly increased in PTB patients; these higher serum levels were correlated with more advanced involvement in chest films and higher bacteria burden in sputum. In multivariate analysis, serum levels of sTREM-1 >260 pg/mL and CRP >2.6 mg/L were independent predictors for on-treatment mortality. Abundant TREM-1-expressing macrophages were identified in lung tissues from PTB samples. In conclusion, serum levels of sTREM-1 correlated with disease severity and treatment outcomes in PTB patients.

Highlights

Despite effective anti-tuberculosis (TB) therapies, TB remains an infectious disease with high morbidity and mortality
Considering the potential synergistic effects of Triggering receptor expressed on myeloid cells 1 (TREM-1) in inflammatory reactions mediated by TLR4 and TLR2, which can recognize Mycobacterium tuberculosis (MTB) components, we hypothesize that triggering receptor expressed on myeloid cells (TREM)-1 is involved in immune responses against MTB
Since the above findings suggested that serum soluble form of TREM-1 (sTREM-1) levels increased in patients with pulmonary TB and significantly correlated with clinical presentations and on-treatment mortality, we further examined TREM-1 expression in lung tissues from two patients with pulmonary TB

Summary

Introduction

Despite effective anti-tuberculosis (TB) therapies, TB remains an infectious disease with high morbidity and mortality Both innate and adaptive immunity are involved in host defense mechanisms against Mycobacterium tuberculosis (MTB) in human lungs. Through a number of receptors on the cell surface, MTB is recognized and ingested by alveolar macrophages, which in turn activate downstream signaling and induce the production of inflammatory cytokines. Engagement of TREM-1 on the cell surface enhances inflammatory reactions, such as cytokine/chemokine production, neutrophil degranulation, and macrophage phagocytosis[8,9]. We measured the serum levels of the soluble forms of TREM-1 and TREM-2 (sTREM-2) in patients with pulmonary TB before initiating anti-TB treatment. The aim of the study was to evaluate the role of sTREMs in clinical presentations and treatment outcomes of pulmonary TB patients. We used immunohistochemistry (IHC) staining to investigate the presence of TREM-1-expressing cells in lung tissues from patients with pulmonary TB

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