title: Schistosome Soluble Egg Antigen Decreases Mycobacterium tuberculosis-Specific CD4+ T-Cell Effector Function With Concomitant Arrest of Macrophage Phago-Lysosome Maturation.
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.
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine Immigrant and Global Health Program, Department of Pediatrics Global Tuberculosis Program.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: DiNardo
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine Department of Pediatrics Center for Immunobiology, Texas Children's Hospital.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Mace
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine Department of Pediatrics Center for Immunobiology, Texas Children's Hospital.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Lesteberg
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Center for Airborne Pathogen Research and Tuberculosis Imaging, Texas A&M Health Science Center, College Station.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Cirillo
authors.affiliation: Immigrant and Global Health Program, Department of Pediatrics Global Tuberculosis Program.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Mandalakas
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Hospital Research Institute.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Graviss
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine Department of Pediatrics Center for Immunobiology, Texas Children's Hospital.
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Orange
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine Department of Pediatrics Center for Immunobiology, Texas Children's Hospital.
authors.forename: George
authors.initials: G
authors.lastname: Makedonas
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance; D007155:Immunologic Factors / Q000378:metabolism*; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology* / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010588:Phagosomes / Q000378:metabolism; D012547:Schistosoma / Q000276:immunology*
chemical_list: D000947:Antigens, Helminth; D016207:Cytokines; D007155:Immunologic Factors
keywords: CD4+ T cells; T-cell function; helminth; high-resolution confocal microscopy; imaging flow cytometry; multiparametric flow cytometry; phago-lysosome maturation; schistosomiasis; tuberculosis