The Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles Medical Center, Torrance, California, USA.
PLoS Pathog. 2009 Dec;5(12):e1000703. doi: 10.1371/journal.ppat.1000703. Epub 2009 Dec 24.
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.
我们旨在定义在免疫接种重组 Als3p（rAls3p-N）疫苗加氢氧化铝（Al（OH（3））佐剂或佐剂对照的小鼠中，对金黄色葡萄球菌和白色念珠菌血流感染的免疫保护机制。IFN-γ缺乏而非 IL-17A 增强了对照小鼠对两种感染的易感性。然而，疫苗诱导的对这两种感染的保护性免疫需要 CD4+T 细胞衍生的 IFN-γ和 IL-17A，以及功能吞噬效应物。疫苗接种可引发 Th1、Th17 和 Th1/17 淋巴细胞，产生促炎细胞因子，增强两种病原体的吞噬杀伤作用。接种感染的小鼠中 IFN-γ、IL-17 和 KC 增加，中性粒细胞浸润增加，组织中病原体负荷减少。总之，rAls3p-N 疫苗接种诱导 Th1/Th17 反应，导致在感染部位招募和激活吞噬细胞，并更有效地清除组织中的金黄色葡萄球菌和白色念珠菌。因此，疫苗介导的适应性免疫可以通过靶向先天效应物来破坏微生物，从而预防这两种感染。
