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: Lin Lin, Ashraf S Ibrahim, Xin Xu, Joshua M Farber, Valentina Avanesian, Beverlie Baquir, Yue Fu, Samuel W French, John E Edwards Jr, Brad Spellberg
• Journal: PLoS pathogens (PLoS Pathog) Vol. 5 Issue 12 Pg. e1000703 (Dec 2009) ISSN: 1553-7374 [Electronic] United States
• PMID: 20041174 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

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

Topics

• Adaptive Immunity
• Adjuvants, Immunologic (pharmacology)
• Adoptive Transfer
• Aluminum Hydroxide (immunology)
• Animals
• Candida albicans (immunology)
• Candidiasis (immunology, 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, prevention & control)
• Staphylococcus aureus (immunology)
• T-Lymphocyte Subsets (immunology)
• Th1 Cells (immunology)
• Vaccines (immunology)