title: Candida albicans stimulates IL-23 release by human dendritic cells and downstream IL-17 secretion by Vδ1 T cells.
abstract: γδ T cells expressing the Vδ1 TCR are expanded in patients with HIV infection. We show in this article that circulating Vδ1 T cell numbers are particularly high in patients with HIV and candidiasis, and that these cells expand and produce IL-17 in response to Candida albicans in vitro. Although C. albicans could directly stimulate IL-17 production by a subset of Vδ1 T cells, fungus-treated dendritic cells (DCs) were required to expand C. albicans-responsive Vδ1 T cells to generate sufficient numbers of cells to release IL-17 at levels detectable by ELISA. C. albicans induced the release of IL-1β, IL-6, and IL-23 by DCs, but addition of these cytokines or supernatants of C. albicans-treated DCs to Vδ1 T cells was not sufficient to induce proliferation. We found that direct contact with DCs was required for Vδ1 T cell proliferation, whereas IL-23R-blocking studies showed that IL-23 was required for optimal C. albicans-induced IL-17 production. Because IL-17 affords protection against both HIV and C. albicans, and because Vδ1 T cells are not depleted by HIV, these cells are likely to be an important source of IL-17 in HIV-infected patients with candidiasis, in whom CD4(+) Th17 responses are impaired. These data show that C. albicans stimulates proliferation and IL-17 production by Vδ1 T cells by a mechanism that involves IL-23 release by DCs.
authors.affiliation: Discipline of Immunology, School of Medicine, Trinity College Dublin, Dublin 8, Ireland;
authors.forename: Christina O
authors.initials: CO
authors.lastname: Maher
authors.affiliation: Discipline of Clinical Microbiology, School of Medicine, Trinity College Dublin, Dublin 8, Ireland; and.
authors.forename: Katie
authors.initials: K
authors.lastname: Dunne
authors.affiliation: Discipline of Clinical Microbiology, School of Medicine, Trinity College Dublin, Dublin 8, Ireland; and.
authors.forename: Ross
authors.initials: R
authors.lastname: Comerford
authors.affiliation: Genitourinary Infectious Diseases Department, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Siobhán
authors.initials: S
authors.lastname: O'Dea
authors.affiliation: Genitourinary Infectious Diseases Department, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Aisling
authors.initials: A
authors.lastname: Loy
authors.affiliation: Genitourinary Infectious Diseases Department, St. James's Hospital, Dublin 8, Ireland.
authors.forename: James
authors.initials: J
authors.lastname: Woo
authors.affiliation: Discipline of Clinical Microbiology, School of Medicine, Trinity College Dublin, Dublin 8, Ireland; and.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Rogers
authors.affiliation: Genitourinary Infectious Diseases Department, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Fiona
authors.initials: F
authors.lastname: Mulcahy
authors.affiliation: Discipline of Immunology, School of Medicine, Trinity College Dublin, Dublin 8, Ireland;
authors.forename: Pádraic J
authors.initials: PJ
authors.lastname: Dunne
authors.affiliation: Discipline of Immunology, School of Medicine, Trinity College Dublin, Dublin 8, Ireland; derek.doherty@tcd.ie.
authors.forename: Derek G
authors.initials: DG
authors.lastname: Doherty
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000276:immunology / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis*; D053759:Interleukin-23 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D053759:Interleukin-23; D016692:Receptors, Antigen, T-Cell, gamma-delta