Abstract

BackgroundMonocytes are the predominant innate immune cells at the early stage of Mycobacterium tuberculosis (M. tb) infection as the host defense against intracellular pathogens. Understanding the profile of different monocyte subpopulations and the dynamics of monocyte-related biomarkers may be useful for the diagnosis and prognosis of tuberculosis.MethodsWe enrolled 129 individuals comprising patients with pulmonary tuberculosis (PTB) (n = 39), tuberculous pleurisy (TBP) (n = 28), malignant pleural effusion (MPE) (n = 21), latent tuberculosis infection (LTBI) (n = 20), and healthy controls (HC) (n = 21). Surface expression of CD14, CD16, and CD163 on monocytes was detected using flow cytometry. In addition, soluble CD163 (sCD163) was determined by enzyme linked immunosorbent assay.ResultsHigher frequency of CD14+CD16+ (15.7% vs 7.8%, P < 0.0001) and CD14−CD16+ (5.3% vs 2.5%, P = 0.0011) monocytes and a decreased percentage of CD14+CD16− (51.0% vs 70.4%, P = 0.0110) cells was observed in PTB patients than in HCs. Moreover, PTB patients displayed a higher frequency of CD163+ cells in CD16+ monocytes than those in the HC group (40.4% vs 11.3%, P < 0.0001). The level of sCD163 was elevated in TBP patients and was higher in pleural effusion than in plasma (2116.0 ng/ml vs 1236.0 ng/ml, P < 0.0001). sCD163 levels in pleural effusion and plasma could be used to distinguish TBP from MPE patients (cut-off values: 1950.0 and 934.7 ng/ml, respectively; AUCs: 0.8418 and 0.8136, respectively). Importantly, plasma sCD163 levels in TBP patients decreased significantly after anti-TB treatment.ConclusionsHigher expression of membrane and soluble CD163 in active tuberculosis patients might provide insights regarding the pathogenesis of tuberculosis, and sCD163 may be a novel biomarker to distinguish TBP from MPE and to predict disease severity.

Highlights

  • Monocytes are the predominant innate immune cells at the early stage of Mycobacterium tuberculosis (M. tb) infection as the host defense against intracellular pathogens

  • We explored the expression of scavenger receptor CD163 on monocyte subsets in populations with different tuberculosis infection statuses including active tuberculosis, latent tuberculosis infection and non-infection, detected the soluble CD163 (sCD163) levels in plasma and pleural effusions, further assessed the value of sCD163 in diagnosing tuberculosis and in predicting the disease severity and treatment outcome

  • Increased percentage of circulating CD16+ monocytes and lack of classical (CD14+CD16−) monocytes in active tuberculosis patients Given the importance of monocytes in the innate immune response to tuberculosis, we investigated the profiles of monocyte subsets in ATB patients based on the expression of CD14 and CD16

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Summary

Introduction

Monocytes are the predominant innate immune cells at the early stage of Mycobacterium tuberculosis (M. tb) infection as the host defense against intracellular pathogens. Monocytes/ macrophages, as the first line of defense, are critical for host immunity against M. tb infection [2,3,4]. Classical monocytes account for the majority of total subsets; they differentiate into proinflammatory M1 macrophages (classical activated) that are permissive to M. tb infection in vitro and produce several pro-inflammatory cytokines [8]. Both non-classical and intermediate monocytes are considered precursors of anti-inflammatory M2 macrophages (alternative activated) in different disease conditions [8]

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