Department of Laboratory Medicine, the Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China.
Department of Laboratory Medicine, the Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China.
Mol Immunol. 2021 Feb;130:37-48. doi: 10.1016/j.molimm.2020.12.019. Epub 2020 Dec 21.
Smalotrophomonas maltophilia(S. maltophilia) is common in nosocomial infections. However, few studies have revealed the effect of S. maltophilia on cellular immunity in the host's immune system up to now. In clinical work, we accidentally discovered that S. maltophilia directly stimulated T cells to secrete IFN-γ.
S. maltophilia was co-cultured with PBMCs to detect secretion of cytokines (IFN-γ, TNF-α and IL-2) and expression of cell surface molecules (CD3, CD4, CD8, CD69, CD147 and CD152) of T cells. We used light microscopy and electron microscopy to observe the cell morphology and subcellular structure of S. maltophilia co-cultured with lymphocytes. Flow cytometry and Western Blot were used to detect the expression of PD-1/PD-L1 and annexin V in cells.
T cells stimulated by S. maltophilia secreted a large amount of IL-2, IFN-γ, and TNF-α. The expression of CD4 and CD8 on the cell surface were declined, accompanied by the activation of the PD-1/PD-L1 pathway, which eventually led to the massive apoptosis of T cells. Electron microscopy showed that cells showed significant apoptotic morphology. Blocking the PD-1/PD-L1 pathway can inhibit the apoptosis-inducing effect of S. maltophilia on T cells.
These indicates that T cells are inhibited after being stimulated by S. maltophilia, and then accelerated to induce death without the initiation of an immunologic cascade. This paper demonstrates for the first time the inhibitory effect of S. maltophilia on cellular immunity, and the immunosuppressive effect induced by infection of S. maltophilia should be considered.
嗜麦芽寡养单胞菌（Smalotrophomonas maltophilia，S. maltophilia）在医院感染中很常见。然而，到目前为止，很少有研究揭示 S. maltophilia 对宿主免疫系统中细胞免疫的影响。在临床工作中，我们偶然发现 S. maltophilia 可直接刺激 T 细胞分泌 IFN-γ。
将 S. maltophilia 与 PBMC 共培养，以检测细胞因子（IFN-γ、TNF-α和 IL-2）的分泌和 T 细胞表面分子（CD3、CD4、CD8、CD69、CD147 和 CD152）的表达。我们使用光学显微镜和电子显微镜观察与淋巴细胞共培养的 S. maltophilia 的细胞形态和亚细胞结构。流式细胞术和 Western Blot 用于检测细胞中 PD-1/PD-L1 和膜联蛋白 V 的表达。
S. maltophilia 刺激的 T 细胞大量分泌 IL-2、IFN-γ和 TNF-α。细胞表面 CD4 和 CD8 的表达下降，同时激活 PD-1/PD-L1 通路，最终导致 T 细胞大量凋亡。电子显微镜显示细胞呈现出明显的凋亡形态。阻断 PD-1/PD-L1 通路可以抑制 S. maltophilia 对 T 细胞的凋亡诱导作用。
这些表明 S. maltophilia 刺激后 T 细胞受到抑制，然后在没有免疫级联反应启动的情况下加速诱导死亡。本文首次证明了 S. maltophilia 对细胞免疫的抑制作用，应该考虑 S. maltophilia 感染引起的免疫抑制作用。
