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Stenotrophomonas-maltophilia inhibits host cellular immunity by activating PD-1/PD-L1 signaling pathway to induce T-cell exhaustion
Molecular Immunology ( IF 3.2 ) Pub Date : 2020-12-21 , DOI: 10.1016/j.molimm.2020.12.019
Min Wang , Sheng Yin , Qi Qin , Yizhi Peng , Zhengang Hu , Xiaolin Zhu , Lei Liu , Xianping Li

Background

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.

Materials and methods

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.

Results

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.

Conclusions

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.



中文翻译:

嗜麦芽窄食单胞菌通过激活PD-1 / PD-L1信号通路诱导T细胞衰竭来抑制宿主细胞免疫

背景

Smalotrophomonas麦芽S.麦芽)是院内感染常见。然而,到目前为止,几乎没有研究揭示嗜麦芽孢杆菌对宿主免疫系统中细胞免疫的影响。在临床工作中,我们意外发现嗜麦芽孢杆菌直接刺激T细胞分泌IFN-γ。

材料和方法

嗜麦芽孢杆菌与PBMC共培养,以检测T细胞的细胞因子(IFN-γ,TNF-α和IL-2)的分泌和细胞表面分子(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嗜麦芽孢杆菌的细胞形态和亚细胞结构。流式细胞仪和Western Blot检测细胞中PD-1 / PD-L1和膜联蛋白V的表达。

结果

嗜麦芽孢杆菌刺激的T细胞分泌大量IL-2,IFN-γ和TNF-α。CD4和CD8在细胞表面的表达下降,伴随着PD-1 / PD-L1途径的激活,最终导致T细胞的大量凋亡。电子显微镜显示细胞显示出明显的凋亡形态。阻断PD-1 / PD-L1途径可以抑制嗜麦芽孢杆菌对T细胞的凋亡诱导作用。

结论

这些表明,T细胞在受到嗜麦芽孢杆菌刺激后被抑制,然后在不引发免疫级联反应的情况下被加速诱导死亡。本文首次证明了嗜麦芽孢杆菌对细胞免疫的抑制作用,应考虑感染嗜麦芽孢杆菌引起的免疫抑制作用。

更新日期:2020-12-22
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