Cátedra de Inmunología, Departamento de Microbiología, Inmunología, Biotecnología y Genética, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Instituto de Estudios de la Inmunidad Humoral "Prof. Ricardo A. Margni" (IDEHU), UBA-CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.
Front Immunol. 2020 Jan 15;10:3008. doi: 10.3389/fimmu.2019.03008. eCollection 2019.
Bacterial superantigens (SAgs) are enterotoxins that bind to MHC-II and TCR molecules, activating as much as 20% of the T cell population and promoting a cytokine storm which enhances susceptibility to endotoxic shock, causing immunosuppression, and hindering the immune response against bacterial infection. Since monocytes/macrophages are one of the first cells SAgs find in infected host and considering the effect these cells have on directing the immune response, here, we investigated the effect of four non-classical SAgs of the staphylococcal operon, namely, SEG, SEI, SEO, and SEM on monocytic-macrophagic cells, in the absence of T cells. We also analyzed the molecular targets on APCs which could mediate SAg effects. We found that SAgs depleted the pool of innate immune effector cells and induced an inefficient activation of monocytic-macrophagic cells, driving the immune response to an impaired proinflammatory profile, which could be mediated directly or indirectly by interactions with MHC class II. In addition, performing surface plasmon resonance assays, we demonstrated that non-classical SAgs bind the gp130 molecule, which is also present in the monocytic cell surface, among other cells.
细菌超抗原（SAg）是一种肠毒素，能够与 MHC-II 和 TCR 分子结合，激活多达 20%的 T 细胞群体，并促进细胞因子风暴，从而增加对内毒素休克的易感性，导致免疫抑制，并阻碍对细菌感染的免疫反应。由于单核细胞/巨噬细胞是 SAg 在感染宿主中首先发现的细胞之一，并且考虑到这些细胞对指导免疫反应的影响，在这里，我们研究了葡萄球菌操纵子的四种非经典 SAg（即 SEG、SEI、SEO 和 SEM）对单核/巨噬细胞的影响，在不存在 T 细胞的情况下。我们还分析了可能介导 SAg 作用的 APC 上的分子靶标。我们发现，SAg 耗尽了先天免疫效应细胞池，并诱导单核/巨噬细胞的低效激活，从而驱动免疫反应呈现受损的促炎表型，这可能通过与 MHC 类 II 的直接或间接相互作用来介导。此外，通过表面等离子体共振分析，我们证明非经典 SAg 结合 gp130 分子，该分子也存在于单核细胞表面以及其他细胞中。
