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- Title
Schistosome Soluble Egg Antigen Decreases Mycobacterium tuberculosis-Specific CD4+ T-Cell Effector Function With Concomitant Arrest of Macrophage Phago-Lysosome Maturation.
- Authors
DiNardo, Andrew R.; Mace, Emily M.; Lesteberg, Kelsey; Cirillo, Jeffrey D.; Mandalakas, Anna M.; Graviss, Edward A.; Orange, Jordan S.; Makedonas, George
- 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.
- Subjects
MYCOBACTERIUM tuberculosis; SCHISTOSOMA; ANTIGENS; T cells; INTERLEUKIN-10; PATIENTS; ANIMALS; CYTOKINES; CYTOPLASM; FLOW cytometry; IMMUNOLOGICAL adjuvants; IMMUNOLOGICAL tolerance; IMMUNOPHENOTYPING; LYSOSOMES; MACROPHAGES; TREMATODA; MONONUCLEAR leukocytes; PHYSIOLOGY
- Publication
Journal of Infectious Diseases, 2016, Vol 214, Issue 3, p479
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiw156