Canadian Center for Vaccinology, Dalhousie University and the IWK Health Centre, Halifax, NS, Canada.
Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
Microbiology (Reading). 2012 Aug;158(Pt 8):2099-2106. doi: 10.1099/mic.0.058073-0. Epub 2012 May 18.
Streptococcus gordonii, a normal inhabitant of the human oral cavity, is a potential live vaccine vehicle. Several pathogen-associated molecular patterns from S. gordonii that are recognized by antigen-presenting cells have recently been identified. In this study, we have identified that the cell-wall-anchored proteins SspA and SspB are immunostimulatory components of S. gordonii. SspA and SspB are members of the antigen I/II family of proteins widely expressed by viridans oral streptococci. The results showed that the mutant (OB219) lacking SspA and SspB had a reduced ability to induce cytokine/chemokine production in epithelial cells and bone-marrow-derived dendritic cells as compared with the parent strain (DL1). Purified SspA induced interleukin-6 and monocyte chemotatic protein-1 production from human lung epithelial A549 cells. The induction could be inhibited by a function-blocking anti-β1 integrin mAb and the purified SspA could bind to β1 integrin precoated on microtitre plates, suggesting that the induction was effected by SspA-β1 integrin interactions. The role of SspA and SspB in innate immunity was further demonstrated in a mouse intranasal challenge experiment, which showed that the clearance of OB219, the recruitment of neutrophils (as indicated by myeloperoxidase activity), and chemokine and cytokine production in the lungs of OB219-inoculated mice were delayed or reduced as compared with the DL1-inoculated mice. In addition to the above, S. gordonii OB219 was more sensitive to polymyxin, nisin and histatin-5 than DL1, suggesting that SspA and SspB also play a role in susceptibility to cationic antimicrobial peptides. Collectively, the results indicate that SspA and SspB are immunostimulatory components of S. gordonii and play an important role in modulating the host's innate immunity.
戈登链球菌是人类口腔的正常寄居者，是一种有潜力的活疫苗载体。最近已经鉴定出几种被抗原呈递细胞识别的来自戈登链球菌的病原体相关分子模式。在这项研究中，我们已经鉴定出细胞壁锚定蛋白 SspA 和 SspB 是戈登链球菌的免疫刺激性成分。SspA 和 SspB 是广泛存在于草绿色链球菌中的抗原 I/II 家族蛋白的成员。结果表明，与亲本菌株（DL1）相比，缺乏 SspA 和 SspB 的突变体（OB219）诱导上皮细胞和骨髓来源的树突状细胞产生细胞因子/趋化因子的能力降低。纯化的 SspA 可诱导人肺上皮细胞 A549 产生白细胞介素-6 和单核细胞趋化蛋白-1。该诱导作用可被功能阻断的抗β1 整合素 mAb 抑制，并且纯化的 SspA 可与预先涂覆在微量滴定板上的β1 整合素结合，表明诱导作用是通过 SspA-β1 整合素相互作用产生的。在小鼠鼻腔挑战实验中进一步证明了 SspA 和 SspB 在固有免疫中的作用，该实验表明，与 DL1 接种的小鼠相比，OB219 接种的小鼠中 OB219 的清除、中性粒细胞的募集（如髓过氧化物酶活性所表明的）以及趋化因子和细胞因子在肺部的产生被延迟或减少。除此之外，与 DL1 相比，S. gordonii OB219 对多粘菌素、乳链菌肽和组蛋白-5 更为敏感，这表明 SspA 和 SspB 也在对抗阳离子抗菌肽的敏感性中发挥作用。总的来说，结果表明 SspA 和 SspB 是戈登链球菌的免疫刺激性成分，在调节宿主固有免疫中发挥重要作用。
