IL-9 Deficiency Promotes Pulmonary Th17 Response in Murine Model of Pneumocystis Infection.
IL-9 Deficiency Promotes Pulmonary Th17 Response in Murine Model of Pneumocystis Infection.
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IL-9 缺乏促进肺孢子虫感染小鼠模型中的肺部 Th17 反应
DOI：
10.3389/fimmu.2018.01118
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发表时间：
2018
影响因子：
7.3
通讯作者：
Tong ZH
中科院分区：
文献类型：
--
作者：
Li T;Rong HM;Zhang C;Zhai K;Tong ZH
肺孢子虫肺炎（PCP）仍然是免疫功能低下患者的严重并发症，死亡率高。CD 4 + T细胞在控制肺孢子虫感染中起着重要作用。Th 9细胞是IL-9的主要来源，在不同的疾病中发挥着多方面的作用。目前尚不清楚IL-9/Th 9是否有助于针对PCP的免疫应答。本研究旨在探讨IL-9在PCP小鼠模型中的作用及其对Th 17细胞的影响。用1 × 106个肺孢子虫经气管内注射建立小鼠肺孢子虫感染模型。肺孢子虫负荷通过TaqMan实时PCR检测。采用IL-9-缺陷（IL-9-/-）小鼠，通过流式细胞术、实时荧光定量PCR和酶联免疫吸附试验（ELISA）研究了肺孢子虫感染后与Th 17应答相关的免疫功能。在感染后3周，与WT小鼠相比，IL-9−/−小鼠的肺孢子虫负荷减少。通过流式细胞仪和实时PCR，IL-9−/−小鼠表现出比WT PCP小鼠更强的Th 17免疫应答。ELISA显示IL-9−/−小鼠的支气管肺泡灌洗液中IL-17和IL-23水平高于WT小鼠。IL-9缺乏可促进CD 4+幼稚T细胞向Th 17细胞分化。IL-17 A中和增加了IL-9−/−小鼠中的肺孢子虫负荷。尽管WT和IL-9−/− PCP小鼠对肺孢子虫的基本清除率相似，但IL-9缺乏可降低肺孢子虫生物负荷，并在感染早期促进肺部Th 17细胞反应。
Pneumocystis pneumonia (PCP) remains a severe complication with high mortality in immunocompromised patients. It has been well accepted that CD4+ T cells play a major role in controlling Pneumocystis infection. Th9 cells were the main source of IL-9 with multifaced roles depending on specific diseases. It is unclear whether IL-9/Th9 contributes to the immune response against PCP. The current study aims to explore the role of IL-9 and the effect of IL-9 on Th17 cells in murine model of PCP. Mice were intratracheally injected with 1 × 106 Pneumocystis organisms to establish the murine model of Pneumocystis infection. Pneumocystis burden was detected by TaqMan real-time PCR. Using IL-9-deficient (IL-9−/−) mice, flow cytometry, real-time PCR and enzyme-linked immunosorbent assay (ELISA) were conducted to investigate the immune function related to Th17 response in defense against Pneumocystis infection. Reduced Pneumocystis burden was observed in lungs in IL-9−/− mice compared with WT mice at 3-week postinfection. IL-9−/−mice exhibited stronger Th17 immune responses than WT PCP mice through flow cytometer and real-time PCR. ELISA revealed higher levels of IL-17 and IL-23 in bronchoalveolar lavage fluid from IL-9−/− mice than WT mice. And IL-9 deficiency promoted Th17 differentiation from CD4+ naive T cells. IL-17A neutralization increased Pneumocystis burden in IL-9−/− mice. Although similar basic clearance of Pneumocystis organisms was achieved in both WT and IL-9−/− PCP mice, IL-9 deficiency could lower Pneumocystis organism burden and promote pulmonary Th17 cells response in the early stage of infection.