Narita Kouji, Hu Dong-Liang, Asano Krisana, Nakane Akio
Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan Institute for Animal Experimentation, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan.
Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan Laboratory of Zoonoses, Kitasato University School of Veterinary Medicine, Towada, Aomori 034-8628, Japan.
Pathog Dis. 2015 Jun;73(4). doi: 10.1093/femspd/ftv023. Epub 2015 Apr 9.
Toxic shock syndrome toxin-1 (TSST-1) is one of superantigens produced by Staphylococcus aureus. We have previously demonstrated that vaccination with non-toxic mutant TSST-1 (mTSST-1) develops host protection to lethal S. aureus infection in mice. However, the detailed mechanism underlying this protection is necessary to elucidate because the passive transfer of antibodies against TSST-1 fails to provide complete protection against S. aureus infection. In this study, the results showed that interleukin-17A (IL-17A)-producing cells were increased in the spleen cells of mTSST-1-vaccinated mice. The main source of IL-17A in mTSST-1-vaccinated mice was T-helper 17 (Th17) cells. The protective effect of vaccination was induced when the vaccinated wild type but not IL-17A-deficient mice were challenged with S. aureus. Gene expression of chemokines, CCL2 and CXCL1, and infiltration of neutrophils and macrophages were increased in spleens and livers of vaccinated mice after infection. The IL-17A-dependent immune response was TSST-1 specific because TSST-1-deficient S. aureus failed to induce the response. The present study suggests that mTSST-1 vaccination is able to provide the IL-17A-dependent host defense against S. aureus infection which promotes chemokine-mediated infiltration of phagocytes into the infectious foci.
中毒性休克综合征毒素-1（TSST-1）是金黄色葡萄球菌产生的超抗原之一。我们之前已经证明，用无毒突变体TSST-1（mTSST-1）进行疫苗接种可使小鼠对致死性金黄色葡萄球菌感染产生宿主保护作用。然而，由于针对TSST-1的抗体被动转移未能提供针对金黄色葡萄球菌感染的完全保护，因此有必要阐明这种保护作用的详细机制。在本研究中，结果显示，接种mTSST-1的小鼠脾细胞中产生白细胞介素-17A（IL-17A）的细胞增加。接种mTSST-1的小鼠中IL-17A的主要来源是辅助性T细胞17（Th17）细胞。当接种疫苗的野生型小鼠而非IL-17A缺陷型小鼠受到金黄色葡萄球菌攻击时，诱导出了疫苗接种的保护作用。感染后，接种疫苗的小鼠脾脏和肝脏中趋化因子CCL2和CXCL1的基因表达以及中性粒细胞和巨噬细胞的浸润增加。IL-17A依赖性免疫反应具有TSST-1特异性，因为缺乏TSST-1的金黄色葡萄球菌无法诱导该反应。本研究表明，mTSST-1疫苗接种能够提供针对金黄色葡萄球菌感染的IL-17A依赖性宿主防御，促进趋化因子介导的吞噬细胞浸润到感染灶中。
