Schistosome Soluble Egg Antigen Decreases Mycobacterium tuberculosis-Specific CD4+ T-Cell Effector Function With Concomitant Arrest of Macrophage Phago-Lysosome Maturation

J Infect Dis. 2016 Aug 1;214(3):479-88. doi: 10.1093/infdis/jiw156. Epub 2016 Apr 18.

Abstract

Helminth-infected individuals possess a higher risk of developing tuberculosis, but the precise immunologic mechanism of Mycobacterium tuberculosis control remains unclear. We hypothesized that a perturbation of the M. tuberculosis-specific CD4(+) T-cell response weakens the ability of macrophages to contain M. tuberculosis We exposed peripheral blood mononuclear cells from M. tuberculosis-infected humans to schistosome soluble egg antigen (SEA) and then profiled M. tuberculosis-specific CD4(+) T cells via multiparametric flow cytometry. SEA decreased the frequency of cells producing interferon γ (6.79% vs 3.20%; P = .017) and tumor necrosis factor α (6.98% vs 2.96%; P = .012), with a concomitant increase in the median fluorescence intensity of interleukin 4 (IL-4; P < .05) and interleukin 10 (IL-10; 1440 vs 1273; P < .05). Macrophages polarized with SEA-exposed, autologous CD4(+) T-cell supernatant had a 2.19-fold decreased colocalization of lysosomes and M. tuberculosis (P < .05). When polarized with IL-4 or IL-10, macrophages had increased expression of CD206 (P < .0001), 1.5-fold and 1.9 fold increased intracellular numbers of M. tuberculosis per macrophage (P < .0005), and 1.4-fold and 1.7-fold decreased colocalization between M. tuberculosis and lysosomes (P < .001). This clarifies a relationship in which helminth-induced CD4(+) T cells disrupt M. tuberculosis control by macrophages, thereby providing a mechanism for the observation that helminth infection advances the progression of tuberculosis among patients with M. tuberculosis infection.

Keywords: CD4+ T cells; T-cell function; helminth; high-resolution confocal microscopy; imaging flow cytometry; multiparametric flow cytometry; phago-lysosome maturation; schistosomiasis; tuberculosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Helminth / metabolism*
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • Cytokines / biosynthesis
  • Flow Cytometry
  • Humans
  • Immune Tolerance
  • Immunologic Factors / metabolism*
  • Immunophenotyping
  • Leukocytes, Mononuclear / immunology
  • Lysosomes / metabolism
  • Macrophages / immunology*
  • Macrophages / microbiology*
  • Macrophages / physiology
  • Mycobacterium tuberculosis / immunology*
  • Phagosomes / metabolism
  • Schistosoma / immunology*

Substances

  • Antigens, Helminth
  • Cytokines
  • Immunologic Factors