title: CD80+Gr-1+ myeloid cells inhibit development of antifungal Th1 immunity in mice with candidiasis.
abstract: To find out whether polymorphonuclear neutrophils (PMN), abundantly recruited in disseminated Candida albicans infection, could directly affect the activation of Th cells we addressed the issues as to whether murine PMN, like their human counterparts, express costimulatory molecules and the functional consequence of this expression in terms of antifungal immune resistance. To this purpose, we assessed 1) the expression of CD80 (B7-1) and CD86 (B7-2) molecules on peripheral, splenic, and inflammatory murine Gr-1+ PMN; 2) its modulation upon interaction with C. albicans in vitro, in vivo, and in human PMN; 3) the effect of Candida exposure on the ability of murine PMN to affect CD4+ Th1 cell proliferation and cytokine production; and 4) the mechanism responsible for this effect. Murine PMN constitutively expressed CD80 molecules on both the surface and intracellularly; however, in both murine and human PMN, CD80 expression was differentially modulated upon interaction with Candida yeasts or hyphae in vitro as well as in infected mice. The expression of the CD86 molecule was neither constitutive nor inducible upon exposure to the fungus. In vitro, Gr-1+ PMN were found to inhibit the activation of IFN-gamma-producing CD4+ T cells and to induce apoptosis through a CD80/CD28-dependent mechanism. A population of CD80+Gr-1+ myeloid cells was found to be expanded in conventional as well as in bone marrow-transplanted mice with disseminated candidiasis, but its depletion increased the IFN-gamma-mediated antifungal resistance. These data indicate that alternatively activated PMN expressing CD80 may adversely affect Th1-dependent resistance in fungal infections.
authors.affiliation: Department of Experimental Medicine and Biochemical Science, University of Perugia, Perugia, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Mencacci
authors.forename: Claudia
authors.initials: C
authors.lastname: Montagnoli
authors.forename: Angela
authors.initials: A
authors.lastname: Bacci
authors.forename: Elio
authors.initials: E
authors.lastname: Cenci
authors.forename: Lucia
authors.initials: L
authors.lastname: Pitzurra
authors.forename: Antonio
authors.initials: A
authors.lastname: Spreca
authors.forename: Manfred
authors.initials: M
authors.lastname: Kopf
authors.forename: Arlene H
authors.initials: AH
authors.lastname: Sharpe
authors.forename: Luigina
authors.initials: L
authors.lastname: Romani
mesh_terms: D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis*; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D018106:CD28 Antigens / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure; D002176:Candida albicans / Q000254:growth & development / Q000276:immunology / Q000648:ultrastructure; D002177:Candidiasis / Q000276:immunology* / Q000473:pathology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000648:ultrastructure; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure; D009569:Nitric Oxide / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology*
chemical_list: D015214:Antigens, Differentiation, Myelomonocytic; D018122:B7-1 Antigen; D018106:CD28 Antigens; D016207:Cytokines; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma