title: Parasite Antigen-Specific Regulation of Th1, Th2, and Th17 Responses in Strongyloides stercoralis Infection.
abstract: Chronic helminth infections are known to be associated with modulation of Ag-specific CD4(+) T responses. However, the role of CD4(+) T cell responses in human infection with Strongyloides stercoralis is not well defined. To examine the role of CD4(+) T cells expressing Th1, Th2, and Th17 cytokines in strongyloidiasis, we compared the frequency (Fo) of these subsets in infected (INF) individuals with Fo in S. stercoralis-uninfected (UN) individuals. INF individuals exhibited a significant decrease in the spontaneous and Ag-specific Fo of both monofunctional and dual-functional Th1 cells compared with UN. Similarly, INF individuals also exhibited significantly decreased Fo of monofunctional and dual-functional Th17 cells upon Ag stimulation compared with UN. In contrast, both the spontaneous and the Ag-induced Fo of monofunctional and dual-functional Th2 cells was significantly increased in INF compared with UN individuals. This differential T cell response was predominantly Ag specific because it was abrogated upon control Ag or mitogen stimulation. The regulation of Th1, Th2, and Th17 cells was predominantly dependent on IL-10, whereas the regulation of Th2, but not Th1 or Th17, cells was also dependent on TGF-β. In addition, treatment of S. stercoralis infection significantly increased the Ag-specific Fo of Th1 and Th17 cells and decreased the Fo of Th2 cells in INF individuals. Thus, S. stercoralis infection is characterized by a parasite Ag-dependent regulation of monofunctional and dual-functional Th1, Th2, and Th17 cells, a regulation also reversible by antihelminthic treatment.
authors.affiliation: National Institutes of Health, International Center for Excellence in Research, Chennai 600031, India;
authors.forename: Rajamanickam
authors.initials: R
authors.lastname: Anuradha
authors.affiliation: National Institutes of Health, International Center for Excellence in Research, Chennai 600031, India;
authors.forename: Saravanan
authors.initials: S
authors.lastname: Munisankar
authors.affiliation: National Institute for Research in Tuberculosis, Chennai 600031, India; and.
authors.forename: Chandrakumar
authors.initials: C
authors.lastname: Dolla
authors.affiliation: National Institute for Research in Tuberculosis, Chennai 600031, India; and.
authors.forename: Paul
authors.initials: P
authors.lastname: Kumaran
authors.affiliation: Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
authors.affiliation: National Institutes of Health, International Center for Excellence in Research, Chennai 600031, India; Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 sbabu@mail.nih.gov.
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D001491:Basophils / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D005260:Female; D005434:Flow Cytometry; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D017171:Strongyloides stercoralis / Q000276:immunology* / Q000502:physiology; D013322:Strongyloidiasis / Q000276:immunology* / Q000469:parasitology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D000947:Antigens, Helminth; D016207:Cytokines; D016212:Transforming Growth Factor beta; D016753:Interleukin-10