Pneumococcal Surface Protein A Plays a Major Role in Streptococcus pneumoniae-Induced Immunosuppression.
Pneumococcal Surface Protein A Plays a Major Role in Streptococcus pneumoniae-Induced Immunosuppression.
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DOI：
10.4049/jimmunol.1502709
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发表时间：
2016-05-01
期刊：
影响因子：
--
通讯作者：
Snapper CM
中科院分区：
文献类型：
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作者：
Saumyaa;Pujanauski L;Colino J;Flora M;Torres RM;Tuomanen E;Snapper CM
完整、灭活的肺炎链球菌(PN)[包括未包裹的菌株R36A]显著抑制对共同免疫的异种蛋白的体液免疫反应，这一特性在其他几种完整的革兰氏阳性或革兰氏阴性细菌中没有观察到。在这项研究中，我们确定了这种免疫抑制特性的性质。由于磷酰胆碱(PC)是PN细胞壁中磷壁酸的主要半抗原成分，而PN膜中的脂磷壁酸先前被报道来自丝虫时具有免疫抑制作用，我们确定了缺乏PC的R36A(R36Apc-)是否具有免疫抑制作用。事实上，尽管R36Apc-对联合免疫CoVA的IgG反应的抑制程度显著降低，但当使用其他几种不同的PC表达细菌或可溶的蛋白质-PC结合物时，没有观察到抑制作用。此外，用高碘酸盐处理R36A，选择性地破坏PC残基，对R36A介导的抑制没有影响。由于R36Apc-也缺乏需要PC附着细胞壁的胆碱结合蛋白(CBPS)，而且由于R36A用胰酶处理消除了其抑制活性，我们将R36A孵育在氯化胆碱中，选择性地将CBPS从其表面剥离。缺乏CBPS的R36A失去了大部分的抑制作用，而含有CBPS的R36A经氯化胆碱处理的上清液具有明显的抑制作用。用Cova和不同的Pn突变体进行的联合免疫研究表明，只有缺乏CBP的Pn，即肺炎球菌表面蛋白A(PSPA)，失去了抑制Ig G抗Cova反应的能力。这些结果有力地表明PSPA在介导PN的免疫抑制特性中起主要作用。
Intact, inactivated Streptococcus pneumoniae (Pn) [including the unencapsulated strain, R36A], markedly inhibits the humoral immune response to co-immunized heterologous proteins, a property not observed with several other intact Gram-positive or Gram-negative bacteria. In this study, we determined the nature of this immunosuppressive property. Since phosphorylcholine (PC), a major haptenic component of teichoic acid in the Pn cell wall, and lipoteichoic acid in the Pn membrane, was previously reported to be immunosuppresive when derived from filarial parasites, we determined whether R36A lacking PC (R36Apc-) was inhibitory. Indeed, although R36Apc- exhibited a markedly reduced level of inhibition of the IgG response to co-immunized cOVA, no inhibition was observed when using several other distinct PC-expressing bacteria or a soluble, protein-PC conjugate. Further, treatment of R36A with periodate, which selectively destroys PC residues, had no effect on R36A-mediated inhibition. Since R36Apc- also lacks choline-binding proteins (CBPs), that require PC for cell wall attachment, and since treatment of R36A with trypsin eliminated its inhibitory activity, we incubated R36A in choline chloride, which selectively strips CBPs from its surface. R36A lacking CBPs lost most of its inhibitory property, whereas the supernatant of choline chloride-treated R36A, containing CBPs, was markedly inhibitory. Co-immunization studies using cOVA and various Pn mutants, each genetically deficient in one of the CBPs, demonstrated that only Pn lacking the CBP, pneumococcal surface protein A (PspA), lost its ability to inhibit the IgG anti-cOVA response. These results strongly suggest that PspA plays a major role in mediating the immunosuppressive property of Pn.