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伯氏考克斯氏体感染中程序性死亡配体-1的表达与记忆性T细胞生成

Programmed death ligand-1 expression and memory T-cell generation in Coxiella burnetii infection.

作者信息

Ka Mignane B, Bechah Yassina, Olive Daniel, Mege Jean-Louis

机构信息

Aix-Marseille University, Unité de Recherche sur les Maladies Infectieuses Transmissibles et Emergentes, UMR 63, CNRS 7278, IRD 198, INSERM U1095, Marseille, France; Inserm UMR 1068, Centre de Recherche en Cancérologie de Marseille, Marseille, France.

Aix-Marseille University, Unité de Recherche sur les Maladies Infectieuses Transmissibles et Emergentes, UMR 63, CNRS 7278, IRD 198, INSERM U1095, Marseille, France.

出版信息

Microb Pathog. 2015 Mar;80:1-6. doi: 10.1016/j.micpath.2015.02.002. Epub 2015 Feb 11.

Abstract

Programmed death ligand-1 (PD-L1) is a co-signaling molecule that regulates T-cell responses in vivo. Its role in bacterial infections, including Q fever, a zoonosis due to Coxiella burnetii infection, is not well understood. We showed by flow cytometry that PD-L1 membrane expression was specifically increased in T-cells from patients with acute Q fever, not from patients with Q fever endocarditis, suggesting that PD-L1 plays a role in the early phases of C. burnetii infection. To assess this hypothesis, we studied the role of PD-L1 in C. burnetii-infected mice. C. burnetii infection resulted in PD-L1 up-regulation in splenocytes. Anti-PD-L1 antibodies injected into the mice did not affect the total number of splenic T-cells but increased the relative number of CD4(+) T-cells compared with CD8(+) T-cells. Additionally, anti-PD-L1 antibodies significantly increased the number of splenic CD4(+) and CD8(+) T cells that expressed low membrane CD62L levels. Our results indicate that the increased expression of PD-L1 by T-cells is associated with a decreased number of memory T-cells during C. burnetii infection, opening new perspectives in the understanding of Q fever pathophysiology.

摘要

程序性死亡配体-1(PD-L1)是一种共信号分子,可在体内调节T细胞反应。其在包括Q热(一种由伯纳特立克次体感染引起的人畜共患病)在内的细菌感染中的作用尚未完全明确。我们通过流式细胞术发现,急性Q热患者的T细胞中PD-L1膜表达特异性增加,而Q热心内膜炎患者的T细胞中则未增加,这表明PD-L1在伯纳特立克次体感染的早期阶段发挥作用。为了验证这一假设,我们研究了PD-L1在感染伯纳特立克次体的小鼠中的作用。伯纳特立克次体感染导致脾细胞中PD-L1上调。给小鼠注射抗PD-L1抗体不会影响脾T细胞的总数,但与CD8(+) T细胞相比,会增加CD4(+) T细胞的相对数量。此外,抗PD-L1抗体显著增加了膜CD62L水平低的脾CD4(+)和CD8(+) T细胞的数量。我们的结果表明,在伯纳特立克次体感染期间,T细胞中PD-L1表达的增加与记忆T细胞数量的减少有关,这为理解Q热病理生理学开辟了新的视角。

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