PD-1 Deficiency Promotes Macrophage Activation and T-Helper Cell Type 1/T-Helper Cell Type 17 Response in Pneumocystis Pneumonia
PD-1 Deficiency Promotes Macrophage Activation and T-Helper Cell Type 1/T-Helper Cell Type 17 Response in Pneumocystis Pneumonia
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PD-1 缺乏促进肺孢子虫肺炎中巨噬细胞激活和 Th1/Th17 反应
DOI：
10.1165/rcmb.2019-0234oc
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发表时间：
2020-06-01
影响因子：
6.4
通讯作者：
Tong, Zhao-Hui
中科院分区：
文献类型：
--
作者：
Zhang, Chao;Rong, Heng-Mo;Tong, Zhao-Hui
肺囊虫是一种罕见的机会性真菌病原体，能够在免疫功能低下的宿主中引起肺囊虫肺炎（PCP）。尽管PCP早在100年前就被发现，但其发病机制仍不清楚。抑制受体PD-1（程序性死亡1）是活化T细胞的负调节因子，据报道参与肿瘤逃逸、免疫耐受和感染免疫。在这项研究中，我们检测了PD-1/PD-L1（程序性死亡配体1）通路在PCP患者和小鼠中的作用。采用实时荧光定量PCR和流式细胞术检测PCP患者和小鼠体内PD-1/PD-L1的表达水平。PD-1（-/-）缺乏的影响在野生型和PD-1小鼠中得到证实。我们的数据显示肺囊虫感染促进PD-1/PD-L1的表达；PD-1缺乏增强了巨噬细胞的吞噬功能和肺t辅助细胞1型(Thl)/Th17反应，这可能有助于肺囊虫的清除；PD-1缺乏会影响巨噬细胞的极化。PCP小鼠经抗pd -1抗体处理后肺囊虫肺清除率提高。总之，我们的研究结果表明，PD-1/PD-L1通路在调节先天和适应性免疫反应中发挥作用，表明操纵该通路可能构成PCP的免疫治疗策略。
Pneumocystis is an unusual, opportunistic fungal pathogen capable of causing Pneumocystis pneumonia (PCP) in immunocompromised hosts. Although PCP was discovered >100 years ago, its pathogenesis remains unclear. The inhibitory receptor PD-1 (programmed death 1), a negative regulator of activated T cells, has been reported to take part in tumor escape, immune tolerance, and infection immunity. In this study, we examined the role of the PD-1/PD-L1 (programmed death-ligand 1) pathway in patients with PCP and in mice. The expression levels of PD-1/PD-L1 in patients with PCP and in mice were measured by real-time PCR and flow cytometry. The effects of PD-1(-/-) deficiency are demonstrated using wild-type and PD-1 mice. Our data show that Pneumocystis infection promotes PD-1/PD-L1 expression; PD-1 deficiency enhances the phagocytic function of macrophages and the pulmonary T-helper cell type 1 (Thl)/Th17 response, which might contribute to Pneumocystis clearance; and PD-1 deficiency affects the polarization of macrophages. PCP mice treated with anti-PD-1 antibody showed improved pulmonary clearance of Pneumocystis. Collectively, our results demonstrate that the PD-1/PD-L1 pathway plays a role in regulating the innate and adaptive immune responses, suggesting that manipulation of this pathway may constitute an immunotherapeutic strategy for PCP.