Department of Microbiology and Immunology, College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, Xinjiang, China.
Department of Microbiology and Immunology, College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, Xinjiang, China.
Microb Pathog. 2021 May;154:104843. doi: 10.1016/j.micpath.2021.104843. Epub 2021 Mar 7.
Staphylococcus aureus (S. aureus) is a frequent and major cause of bovine mastitis; it poses a tremendous economic burden to dairy industries of numerous countries. Early-secretion antigen-6 secretion system (ESS) has been viewed as an essential virulence and pathogenic factor of S. aureus. EsxA and EsxB are small acidic proteins secreted by ESS and identified as potential T-cell antigens of S. aureus. Unlike those of Mycobacterium tuberculosis (M. tuberculosis), the EsxA and EsxB of S. aureus do not form a dimer. Instead, EsxA dimerizes with itself or EsaC. Therefore, the interaction of EsxA and EsxB remains incompletely understood. In this study, to explore their interactions, EsxA and EsxB were expressed and used for immunization, alone or in combination, of murine infection models. Both components can interact with each other. Through the analysis of the immune response by immunological method, EsxB could significantly enhance the EsxA-specific IgG2a antibody level and increase the proliferation proportion of CD8 T cells. These results indicate that when vaccinated with EsxA, EsxB can play a critical role in stimulating T helper 1 immunity by activating IgG2a and CD8 T cells. We further show that vaccination with the combination of EsxA and EsxB resulted in enhanced stimulation of TLR-4 and improved protection against S. aureus. The findings may help us better understand the role of EsxB in the virulence and pathogenesis of S. aureus.
金黄色葡萄球菌（S. aureus）是牛乳腺炎的常见且主要原因；它给许多国家的奶制品行业带来了巨大的经济负担。早期分泌抗原-6 分泌系统（ESS）被视为 S. aureus 的重要毒力和致病因素。EsxA 和 EsxB 是由 ESS 分泌的小酸性蛋白，被鉴定为 S. aureus 的潜在 T 细胞抗原。与结核分枝杆菌（M. tuberculosis）不同，S. aureus 的 EsxA 和 EsxB 不形成二聚体。相反，EsxA 与自身或 EsaC 二聚化。因此，EsxA 和 EsxB 的相互作用仍不完全清楚。在这项研究中，为了探索它们的相互作用，单独或组合表达和使用 EsxA 和 EsxB 进行了小鼠感染模型的免疫接种。这两个组件可以相互作用。通过免疫方法分析免疫反应，EsxB 可以显著提高 EsxA 特异性 IgG2a 抗体水平，并增加 CD8 T 细胞的增殖比例。这些结果表明，当用 EsxA 接种疫苗时，EsxB 通过激活 IgG2a 和 CD8 T 细胞在刺激辅助性 T 细胞 1 免疫中起关键作用。我们进一步表明，用 EsxA 和 EsxB 的组合进行疫苗接种可增强 TLR-4 的刺激，并改善对 S. aureus 的保护。这些发现可能有助于我们更好地理解 EsxB 在 S. aureus 毒力和发病机制中的作用。
