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

作者：DiNardo Andrew R; Mace Emily M; Lesteberg Kelsey; Cirillo Jeffrey D; Mandalakas Anna M; Graviss Edward A; Orange Jordan S; Makedonas George^*

来源：Journal of Infectious Diseases, 2016, 214(3): 479-488.

DOI：10.1093/infdis/jiw156

• tuberculosis
• schistosomiasis
• helminth
• CD4(+) T cells
• T-cell function
• multiparametric flow cytometry
• phago-lysosome maturation
• high-resolution confocal microscopy
• imaging flow cytometry

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 gamma (6.79% vs 3.20%; P = .017) and tumor necrosis factor a (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.

• 出版日期2016-8-1