Th1-Th17 Cells Mediate Protective Adaptive Immunity Against Staphylococcus Aureus and Candida Albicans Infection in Mice

PLoS Pathog. 2009 Dec;5(12):e1000703. doi: 10.1371/journal.ppat.1000703. Epub 2009 Dec 24.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adaptive Immunity*
  • Adjuvants, Immunologic / pharmacology
  • Adoptive Transfer
  • Aluminum Hydroxide / immunology
  • Animals
  • Candida albicans / immunology
  • Candidiasis / immunology*
  • Candidiasis / prevention & control
  • Female
  • Fungal Proteins / immunology*
  • Fungal Vaccines / immunology*
  • Interferon-gamma
  • Interleukin-17 / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / prevention & control
  • Staphylococcus aureus / immunology
  • T-Lymphocyte Subsets / immunology*
  • Th1 Cells / immunology
  • Vaccines / immunology

Substances

  • ALS3 protein, Candida albicans
  • Adjuvants, Immunologic
  • Fungal Proteins
  • Fungal Vaccines
  • Interleukin-17
  • Vaccines
  • Aluminum Hydroxide
  • Interferon-gamma