title: Interleukin 1 (IL-1)- and IL-23-mediated expansion of filarial antigen-specific Th17 and Th22 cells in filarial lymphedema.
abstract: Lymphatic filarial disease is known to be associated with elevated Th1 responses and normal or diminished Th2 responses to parasite-specific antigens. The roles of Th17 cells and the recently described Th22 cells have not been examined in detail in either filarial infection itself or in filarial disease (e.g., lymphedema and elephantiasis). To explore the roles of Th17 and Th22 cells and their subsets, we examined the frequencies of these cells in individuals with filarial lymphedema (chronic pathology [CP]), in clinically asymptomatic infected (INF) individuals, and in uninfected (UN) individuals ex vivo and in response to parasite and nonparasite antigens. Those with disease (CP) had significantly expanded frequencies of Th17 and Th22 cells, compared with either INF or UN individuals, at baseline (ex vivo) and in response to parasite antigens. This antigen-driven expansion of Th17 and Th22 cells was dependent on interleukin 1 (IL-1), IL-23, and, to lesser extent, transforming growth factor β (TGF-β), as blockade of any of these cytokines resulted in significantly diminished frequencies of Th17 and Th22 cells. Our findings, therefore, suggest that filarial parasite-driven expansion of Th17 and Th22 cells is associated with the pathogenesis of filarial infections and disease.
authors.affiliation: National Institutes of Health, International Center for Excellence in Research, Chennai, India.
authors.forename: R
authors.initials: R
authors.lastname: Anuradha
authors.affiliation: National Institutes of Health, International Center for Excellence in Research, Chennai, India.
authors.forename: P Jovvian
authors.initials: PJ
authors.lastname: George
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: V
authors.initials: V
authors.lastname: Chandrasekaran
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: P Paul
authors.initials: PP
authors.lastname: Kumaran
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
authors.affiliation: National Institutes of Health, International Center for Excellence in Research, Chennai, India Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA sbabu@mail.nih.gov.
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
mesh_terms: D000818:Animals; D017178:Brugia malayi / Q000276:immunology; D004605:Elephantiasis, Filarial / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology; D014958:Wuchereria bancrofti / Q000276:immunology
chemical_list: D007375:Interleukin-1; D053759:Interleukin-23; D016212:Transforming Growth Factor beta