Low-Density Granulocytes Are Elevated in Mycobacterial Infection and Associated with the Severity of Tuberculosis

PLoS One. 2016 Apr 13;11(4):e0153567. doi: 10.1371/journal.pone.0153567. eCollection 2016.

Abstract

Tuberculosis remains a global health problem caused by infection with Mycobacterium tuberculosis. Numerous studies have established a close correlation between the development of tuberculosis and the roles of neutrophils. Recently, a distinct population of CD15+ granulocytes was found to be present in the peripheral blood mononuclear cell (PBMC) fraction in humans. This population of granulocytes, termed low-density granulocytes (LDGs), was reported to be elevated and associated with disease activity or severity in a number of different conditions including SLE, asthma and HIV infection. However, both the frequency and clinical significance of LDGs associated with tuberculosis are unclear. Here we determined LDG levels and made comparisons between subjects with active pulmonary tuberculosis (PTB) and healthy controls, between PTB patients with mild-to-moderate disease and patients with advanced disease, and among PTB patients following anti-tuberculous therapy of varying durations. The direct correlation between M. tuberculosis infection and LDG levels was confirmed by in vitro infection of whole peripheral blood and isolated granulocytes with mycobacteria. Our results demonstrated that PBMCs in PTB patients contained significantly elevated percentages of LDGs compared with control subjects. LDGs in tuberculosis expressed higher levels of activation markers compared to normal-density granulocytes (NDGs). M. tuberculosis induced the generation of LDGs in both whole blood and isolated NDGs from control subjects, which suggests that LDGs associated with M. tuberculosis infection are likely to originate from in situ activation. Furthermore, our results revealed that the frequency of LDGs is associated with the severity of tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Granulocytes / metabolism
  • Granulocytes / pathology*
  • Humans
  • Leukocyte Count
  • Lewis X Antigen / metabolism
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis
  • Reactive Oxygen Species / metabolism
  • Severity of Illness Index
  • Tuberculosis, Pulmonary / pathology*

Substances

  • Lewis X Antigen
  • Reactive Oxygen Species

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant numbers: 81060001 and 81170006 to L.J.-M.). URL of NSFC: http://www.nsfc.gov.cn. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.