隐球菌性脑膜炎患者外周血中Th9和Th17细胞水平变化及意义

中国真菌学杂志　 2014, Vol. 9 　Issue (2): 79-82,95.

隐球菌性脑膜炎患者外周血中Th9和Th17细胞水平变化及意义

雷文知, 桑军军, 潘炜华, 廖万清

上海长征医院皮肤病与真菌病研究所全军真菌病重点实验室第二军医大学附属长征医院皮肤科, 上海 200003

收稿日期:2014-03-04 出版日期:2014-04-28 发布日期:2014-04-28
通讯作者: 廖万清，liaowanqing@sohu.com E-mail:liaowanqing@sohu.com
作者简介:雷文知，女（汉族），博士研究生在读，主治医师.E-mail：leiwenzhi08@126.com

Expression and significance of Th9 and Th17 in the peripheral blood of patients with cryptococcal meningitis

LEI Wen-zhi, SANG Jun-jun, PAN Wei-hua, LIAO Wan-qing

Department of dermatology, Changzheng Hospital.Institute of dermatology and medical mycology, Changzheng Hospital.Key laboratory of molecular medical mycology, PLA key laboratory of medical mycology, Shanghai 200003

Received:2014-03-04 Online:2014-04-28 Published:2014-04-28

摘要/Abstract

摘要：

目的比较初发隐球菌性脑膜炎患者治疗前后与健康对照人群外周血CD4+T细胞中Th9和Th17细胞的比值，探讨Th9和Th17细胞在隐球菌性脑膜炎发病机制中的作用。方法选取初发未经治疗隐球菌性脑膜炎患者及健康对照各12例，抽取隐球菌性脑膜炎患者治疗前和治疗后3周及健康对照的外周血，分离外周血单核细胞，应用流式细胞仪检测技术对3组病例外周血CD4+T细胞中Th9和Th17的比值进行比较。结果与健康对照相比，隐球菌性脑膜炎患者治疗前Th17表达下调，差异有统计学意义；在治疗好转患者中，治疗后Th17表达显著上调，与治疗前及健康对照相比差异均有统计学意义。Th9在治疗前与健康对照相比无差异，在治疗后隐球菌性脑膜炎患者中表达上调。结论 Th17免疫途径是隐球菌性脑膜炎患者抵御隐球菌感染的重要免疫机制，隐球菌性脑膜炎发病及治疗拮抗可能与Th17缺乏有关。

关键词: 隐球菌性脑膜炎, 辅助T细胞, Th17, Th9, 隐球菌

Abstract:

Objective To explore the role of Th9 and Th17 cells in the pathogenesis of CM by mesureing the ratio of Th9 and Th17 cells in CD4+T lymphocyte of patients with cryptococcal meningitis (CM).Methods Twelve CM patients without antifungal treatment and 12 healthy controls were selected. The peripheral blood was collected from patients prior treatment and three weeks after treatment and the healthy controls. The ratio of Th9 and Th17 cells in peripheral blood were analyzed by flow cytometry.Result The ratio of Th17 cells in patients with CM before treatment was less than those of healthy people, and patients who received treatment showed the increased level of Th17 cells which was higher than those in patients before treatment and the healthy controls. The ratioof Th9 also increased in the patients who received treatment while there was no significant different between the patients before treatment and the healthy controls.Conclusion Th17 immune pathway is an important immune mechanism against Cryptococcus infection in patients with CM. The lack of Th17 cells may play a role in the pathogenesis and treatment-resistant of CM.

Key words: cryptococcal meningitis, Th cells, Th17, Th9, Cryptococcus

中图分类号:

R519.4

雷文知, 桑军军, 潘炜华, 廖万清. 隐球菌性脑膜炎患者外周血中Th9和Th17细胞水平变化及意义[J]. 中国真菌学杂志, 2014, 9(2): 79-82,95.

LEI Wen-zhi, SANG Jun-jun, PAN Wei-hua, LIAO Wan-qing. Expression and significance of Th9 and Th17 in the peripheral blood of patients with cryptococcal meningitis[J]. Chinese Journal of Mycology, 2014, 9(2): 79-82,95.

参考文献

[1] Park BJ, Wannemuehler KA, Marston BJ,et al. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS[J]. AIDS (London, England),2009,23(4): 525-530.
[2] Veldhoen M, Uyttenhove C, van Snick J, et al. Transforming growth factor-beta‘reprograms’the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset[J]. Nat Immunol,2008,9(12): 1341-1346.
[3] Khader SA, Cooper AM. IL-23 and IL-17 in tuberculosis[J]. Cytokine,2008,41(2): 79-83.
[4] Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells[J]. Nature,2006,441(7090): 235-238.
[5] Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america[J]. Clin Infect Dis,2010,50(3): 291-322.
[6] Charlier C, Nielsen K, Daou S,et al. Evidence of a role for monocytes in dissemination and brain invasion by Cryptococcus neoformans[J]. Infect Immun, 2009,77(1): 120-127.
[7] Tan DB, Yong YK, Tan HY, et al. Immunological profiles of immune restoration disease presenting as mycobacterial lymphadenitis and cryptococcal meningitis[J]. HIV Med,2008,9(5): 307-316.
[8] Schop J. Protective immunity against cryptococcus neoformans infection[J]. Mcgill J Med,2007,10(1): 35-43.
[9] Dardalhon V, Awasthi A, Kwon H, et al. IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells[J]. Nat Immunol,2008, 9(12): 1347-1355.
[10] Guzman-Fulgencio M, Jimenez JL, Berenguer J, et al. Plasma IL-6 and IL-9 predict the failure of interferon-alpha plus ribavirin therapy in HIV/HCV-coinfected patients[J]. J Antimicrob Chemother,2012,67(5): 1238-1245.
[11] Zelante T, De Luca A, Bonifazi P, et al. IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance[J]. Eur J Immunol,2007,37(10): 2695-2706.
[12] Khader SA, Bell GK, Pearl JE, et al. IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge[J]. Nat Immunol,2007,8(4): 369-377.
[13] Murdock BJ, Huffnagle GB, Olszewski MA,et al. Interleukin-17A Enhances Host Defense against Cryptococcal Lung Infection through Effects Mediated by Leukocyte Recruitment, Activation, and Gamma Interferon Production[J]. Infect Immun,2014, 82(3): 937-948.
[14] Beriou G, Bradshaw EM, Lozano E, et al. TGF-beta induces IL-9 production from human Th17 cells[J]. J Immunol,2010,185(1): 46-54.
[15] Nowak EC, Weaver CT, Turner H, et al. IL-9 as a mediator of Th17-driven inflammatory disease[J]. J Exp Med,2009,206(8): 1653-1660.
[16] Qiu Y, Davis MJ, Dayrit JK, et al. Immune modulation mediated by cryptococcal laccase promotes pulmonary growth and brain dissemination of virulent Cryptococcus neoformans in mice[J]. PLoS One,2012,7(10): e47853.
[17] Ye P, Garvey PB, Zhang P, et al. Interleukin-17 and lung host defense against Klebsiella pneumoniae infection[J]. Am J Respir Cell Mol Biol,2001,25(3): 335-340.
[18] Turner JE, Morrison PJ, Wilhelm C, et al. IL-9-mediated survival of type 2 innate lymphoid cells promotes damage control in helminth-induced lung inflammation[J]. J Exp Med,2013,210(13): 2951-2965.