Th1-Th17 cells mediate protective adaptive immunity against Staphylococcus aureus and Candida albicans infection in mice.
Th1-Th17 cells mediate protective adaptive immunity against Staphylococcus aureus and Candida albicans infection in mice.
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DOI：
10.1371/journal.ppat.1000703
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发表时间：
2009-12
期刊：
影响因子：
6.7
通讯作者：
Spellberg B
中科院分区：
文献类型：
--
作者：
Lin L;Ibrahim AS;Xu X;Farber JM;Avanesian V;Baquir B;Fu Y;French SW;Edwards JE Jr;Spellberg B
我们试图确定用重组 N 端 Als3p (rAls3p-N) 疫苗加氢氧化铝 (Al(OH3)) 佐剂或佐剂对照免疫的小鼠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 的缺乏而非 IL-17A 的缺乏增强了对照小鼠对这两种感染的易感性。然而，针对这两种感染的疫苗诱导的保护性免疫需要 CD4+ T 细胞衍生的 IFN-γ 和 IL-17A 以及功能性吞噬效应细胞引发了 Th1、Th17 和 Th1/17 淋巴细胞，这些细胞产生了增强对两种生物体的吞噬杀伤的促炎细胞因子。接种疫苗的受感染小鼠的 IFN-γ、IL-17 和 KC 增加，中性粒细胞流入增加，组织中的生物体负担减少。诱导 Th1/Th17 反应，导致感染部位吞噬细胞的募集和激活，并更有效地从组织中清除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先天效应子消灭金黄色葡萄球菌和真菌念珠菌，从而预防这两种感染。预防此类感染的疫苗将具有巨大的公共卫生意义。解释为什么尚未成功开发出针对这些感染的疫苗的主要假设是，引起感染的微生物非常复杂，并使用多种武器（所谓的“毒力因子”）在人类中引起疾病，因此，针对任一感染的疫苗必须同时中和许多这些毒力因子。我们的疫苗基于念珠菌使用的单一毒力因子，其形状与所使用的毒力因子相似。在目前的研究中，我们报告说，我们的疫苗可以诱导免疫系统中的特殊细胞更有效地调用增强剂来杀死生物体。这些数据表明，即使它们不能通过中和多种毒力因子来发挥作用，也可以开发出针对这两种生物体的疫苗，从而为开发更广泛的针对这两种感染的疫苗类型打开了大门。
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. The bacterium Staphylococcus aureus and the fungus Candida are the second and third leading cause of bloodstream infections in hospitalized patients. A vaccine to prevent such infections would be of enormous public health benefit. The leading hypothesis to explain why vaccines have not been successfully developed against these infections is that the microbes causing the infections are highly complex, and use multiple weapons (so-called “virulence factors”) to cause disease in humans. Therefore, a vaccine targeting either infection would have to neutralize many of these virulence factors at the same time. We have been developing a vaccine that simultaneously targets both types of infections. Our vaccine is based on a single virulence factor used by Candida, which has a similar shape to virulence factors used by S. aureus. In the current study, we report that our vaccine induces specialized cells in the immune system to more effectively call in reinforcements to kill the organisms. These data demonstrate that vaccines against both organisms can be developed even if they do not work by neutralizing multiple virulence factors, and therefore open the door to a far wider array of vaccine types against both infections.
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影响因子：
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