Th1-Th17 cells mediate protective adaptive immunity against Staphylococcus aureus and Candida albicans infection in mice.
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.
Lin
Lin
L
The Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles Medical Center, Torrance, California, USA.
Ibrahim
Ashraf S
AS
Xu
Xin
X
Farber
Joshua M
JM
Avanesian
Valentina
V
Baquir
Beverlie
B
Fu
Yue
Y
French
Samuel W
SW
Edwards
John E
JE
Spellberg
Brad
B
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
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