title: Th1-Th17 cells mediate protective adaptive immunity against Staphylococcus aureus and Candida albicans infection in mice.
abstract: We sought to define protective mechanisms of immunity to Staphylococcus aureus and Candida albicans bloodstream infections in mice immunized with the recombinant N-terminus of Als3p (rAls3p-N) vaccine plus aluminum hydroxide (Al(OH(3)) adjuvant, or adjuvant controls. Deficiency of IFN-gamma but not IL-17A enhanced susceptibility of control mice to both infections. However, vaccine-induced protective immunity against both infections required CD4+ T-cell-derived IFN-gamma and IL-17A, and functional phagocytic effectors. Vaccination primed Th1, Th17, and Th1/17 lymphocytes, which produced pro-inflammatory cytokines that enhanced phagocytic killing of both organisms. Vaccinated, infected mice had increased IFN-gamma, IL-17, and KC, increased neutrophil influx, and decreased organism burden in tissues. In summary, rAls3p-N vaccination induced a Th1/Th17 response, resulting in recruitment and activation of phagocytes at sites of infection, and more effective clearance of S. aureus and C. albicans from tissues. Thus, vaccine-mediated adaptive immunity can protect against both infections by targeting microbes for destruction by innate effectors.
authors.affiliation: The Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles Medical Center, Torrance, California, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.forename: Ashraf S
authors.initials: AS
authors.lastname: Ibrahim
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Farber
authors.forename: Valentina
authors.initials: V
authors.lastname: Avanesian
authors.forename: Beverlie
authors.initials: B
authors.lastname: Baquir
authors.forename: Yue
authors.initials: Y
authors.lastname: Fu
authors.forename: Samuel W
authors.initials: SW
authors.lastname: French
authors.forename: John E
authors.initials: JE
authors.lastname: Edwards
authors.forename: Brad
authors.initials: B
authors.lastname: Spellberg
mesh_terms: D056704:Adaptive Immunity; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D019264:Adoptive Transfer; D000536:Aluminum Hydroxide / Q000276:immunology; D000818:Animals; D002176:Candida albicans / Q000276:immunology; D002177:Candidiasis / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D005656:Fungal Proteins / Q000276:immunology*; D005657:Fungal Vaccines / Q000276:immunology*; D007371:Interferon-gamma; D020381:Interleukin-17 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013203:Staphylococcal Infections / Q000276:immunology* / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014612:Vaccines / Q000276:immunology
chemical_list: C113620:ALS3 protein, Candida albicans; D000276:Adjuvants, Immunologic; D005656:Fungal Proteins; D005657:Fungal Vaccines; D020381:Interleukin-17; D014612:Vaccines; D000536:Aluminum Hydroxide; D007371:Interferon-gamma