Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan.
Infect Immun. 2010 Oct;78(10):4234-42. doi: 10.1128/IAI.00447-10. Epub 2010 Aug 2.
Clumping factor A (ClfA) is a fibrinogen-binding cell wall-attached protein and an important virulence factor of Staphylococcus aureus. Previous studies reported that an immunization with the fibrinogen-binding domain of ClfA (ClfA(40-559)) protected animals against S. aureus infection. It was reported that some cytokines are involved in the pathogenesis of staphylococcal diseases and in host defense against S. aureus infection. However, the role of cytokines in the protective effect of ClfA(40-559) as a vaccine has not been elucidated. In this study, we demonstrated that the spleen cells of ClfA(40-559)-immunized mice produced a large amount of interleukin-17A (IL-17A). The protective effect of immunization was exerted in wild-type mice but not in IL-17A-deficient mice. IL-17A mRNA expression was increased in the spleens and kidneys of immunized mice after infection. CXCL2 and CCL2 mRNA expression was increased in the spleens and kidneys, respectively. Consistent with upregulation of the mRNA expression, neutrophils infiltrated into the spleens extensively and macrophage infiltration was observed in the kidneys of immunized mice. These results suggest that immunization with ClfA(40-559) induces the IL-17A-producing cells and that IL-17-mediated cellular immunity is involved in the protective effect induced by immunization with ClfA(40-559) against S. aureus infection.
凝聚因子 A(ClfA)是一种纤维蛋白原结合的细胞壁附着蛋白,也是金黄色葡萄球菌的重要毒力因子。先前的研究表明,用 ClfA 的纤维蛋白原结合结构域(ClfA(40-559))免疫可以保护动物免受金黄色葡萄球菌感染。据报道,一些细胞因子参与了葡萄球菌病的发病机制以及宿主对金黄色葡萄球菌感染的防御。然而,细胞因子在 ClfA(40-559)作为疫苗的保护作用中的作用尚未阐明。在这项研究中,我们证明了 ClfA(40-559)免疫小鼠的脾细胞产生了大量的白细胞介素-17A(IL-17A)。免疫的保护作用仅在野生型小鼠中发挥,而在 IL-17A 缺陷型小鼠中则不发挥。感染后,免疫小鼠的脾脏和肾脏中 IL-17A mRNA 表达增加。脾脏和肾脏中分别增加了 CXCL2 和 CCL2 的 mRNA 表达。与 mRNA 表达的上调一致,大量中性粒细胞浸润到脾脏中,并且在免疫小鼠的肾脏中观察到巨噬细胞浸润。这些结果表明,用 ClfA(40-559)免疫可诱导产生产生 IL-17A 的细胞,并且 IL-17 介导的细胞免疫参与了用 ClfA(40-559)免疫诱导的针对金黄色葡萄球菌感染的保护作用。