Th1-Th17 Cells Mediate Protective Adaptive Immunity against Staphylococcus aureus and Candida albicans Infection in Mice

PLoS Pathogens

Valentina Avanesian¹  Joshua M. Farber¹  Xin Xu²  John E. Edwards Jr.²  Brad Spellberg²  Lin Lin³  Ashraf S. Ibrahim³  Samuel W. French³  Beverlie Baquir³  Yue Fu³ 

[1] Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America;The David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America;The Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, California, United States of America

关键词: C;    ida albicans;    Staphylococcus aureus;    Vaccines;    Lymphocytes;    Cytokines;    Neutrophils;    Vaccination;    immunization;    T cells;   

DOI  :  10.1371/journal.ppat.1000703

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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(OH3) adjuvant, or adjuvant controls. Deficiency of IFN-γ 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-γ 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-γ, 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.

【 授权许可】

CC BY