title: Abrogation of spontaneous liver tolerance during immune response to Candida albicans: contribution of NKT and hepatic mononuclear cells.
abstract: Hepatic mononuclear cells (HMC) are a heterogeneous population with innate immune properties involved in the response to several pathogens. Herein, during the primary infection with Candida albicans, we observed dynamic changes in CD3+, NK+ and NKT+ intrahepatic lymphoid subsets and a significant increase in the absolute number of antigen-presenting cells (APC). The liver tolerogenic microenvironment sustained by higher levels of IL-10, transforming growth factor-β and IL-4 was severely modified upon the robust IFN-γ production after the fungal colonization. NKT cells purified from infected animals released significant amounts of IFN-γ and the production of this cytokine was exacerbated after a second contact with the fungus. Interestingly, C. albicans per se was unable to activate tolerogenic NKT cells from naive animals. In vitro experiments performed with HMC cells depleted of the CD11b/c+ population revealed that in the absence of APC, NKT cells are unable to produce IFN-γ in response to C. albicans. Our findings constitute the first evidence that this innate lymphocyte population is involved in the pathogenesis of C. albicans infection.
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI)-Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: María Sol
authors.initials: MS
authors.lastname: Renna
authors.forename: Carlos Mauricio
authors.initials: CM
authors.lastname: Figueredo
authors.forename: María Cecilia
authors.initials: MC
authors.lastname: Rodríguez-Galán
authors.forename: Paula Alejandra
authors.initials: PA
authors.lastname: Icely
authors.forename: Javier María
authors.initials: JM
authors.lastname: Peralta Ramos
authors.forename: Silvia Graciela
authors.initials: SG
authors.lastname: Correa
authors.forename: Claudia Elena
authors.initials: CE
authors.lastname: Sotomayor
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000276:immunology* / Q000472:pathogenicity; D002177:Candidiasis / Q000276:immunology* / Q000382:microbiology*; D005260:Female; D005434:Flow Cytometry; D022781:Hepatocytes / Q000276:immunology*; D007113:Immunity, Innate; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D055611:Natural Killer T-Cells / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar