Chronic Chagas' disease cardiomyopathy patients display an increased IFN-γ response to Trypanosoma cruzi infection
Chronic Chagas' disease cardiomyopathy patients display an increased IFN-γ response to Trypanosoma cruzi infection
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DOI：
10.1006/jaut.2001.0523
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发表时间：
2001-08-01
影响因子：
12.8
通讯作者：
Cunha-Neto, E
中科院分区：
文献类型：
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作者：
Abel, LCJ;Rizzo, LV;Cunha-Neto, E
在所有克氏锥虫感染的患者中，有三分之一最终发展为慢性恰加斯病心肌病(CCC)，这是一种特别致命的炎症性扩张性心肌病，寄生虫稀少，心脏浸润性单个核细胞似乎是组织损伤的效应者。由于T CRUZI是产生IL-12的主要诱导物，因此我们探讨了炎性细胞因子在CCC发病机制中的作用。我们检测了CCC和无症状T细胞感染(ASY)患者外周血单个核细胞(PBMC)以及来自CCC患者心内膜心肌活检组织的T细胞株产生的细胞因子。CCC和ASY患者的PBMC对B13蛋白和植物血凝素PHA的反应水平高于正常人(N)；CCC患者高应答者(大于或等于1 ng/ml)的频率是ASY患者的2-3倍。相反，在感染了克鲁兹旋毛虫的患者中，对相同刺激的反应产生的IL-4被抑制。PHA诱导PBMC产生干扰素-γ的频率在CCC组显著高于ASY组和N组。10株PHA刺激的CCC患者T细胞株产生干扰素-γ和肿瘤坏死因子-α，4/10株和1/10株产生IL-2和IL-10，IL-4、IL-1α、IL-1β、IL-6和IL-12检测不到。我们的结果表明，CCC和ASY患者对克氏毛滴虫感染提供的干扰素-γ诱导刺激的反应可能不同。考虑到来自CCC患者的心脏浸润性T细胞系的T-1型细胞因子谱，启动强烈的干扰素-γ反应的能力可能在CCC发生的不同易感性中发挥作用。(C)2001年学术出版社。
One-third of all Trypanosoma cruzi-infected patients eventually develop chronic Chagas' disease cardiomyopathy (CCC), a particularly lethal inflammatory dilated cardiomyopathy, where parasites are scarce and heart-infiltrating mononuclear cells seem to be the effectors of tissue damage. Since T cruzi is a major inducer of interleukin-12 production, the role of inflammatory cytokines in the pathogenesis of CCC was investigated. We assayed cytokine production by peripheral blood mononuclear cells (PBMC) from CCC and asymptomatic T cruzi-infected (ASY) individuals, as well as by T cell lines from endomyocardial biopsies from CCC patients. PBMC from CCC and ASY patients produced higher IFN-gamma levels than normal (N) individuals in response to B13 protein and phytohaemagglutinin PHA; IFN-gamma high responders (greater than or equal to1 ng/ml) were 2-3 fold more frequent among CCC patients than ASY individuals. Conversely, IL-4 production in response to the same stimuli was suppressed among T. cruzi-infected patients. The frequency of PHA-induced IFN gamma -producing cells on PBMC was significantly higher among CCC than ASY and N individuals. IFN-gamma and TNF-a were produced by ten out of ten PHA-stimulated T cell lines from CCC patients; IL-2 and IL-10 were produced by four out of ten and one out of ten lines, respectively; IL-4, IL-1 alpha, IL-1 beta, IL-6 and IL-12 were undetectable. Our results suggest that CCC and ASY patients may respond differentially to the IFN-gamma -inducing stimulus provided by T. cruzi infection. Given the T-1-type cytokine profile of heart-infiltrating T cell lines from CCC patients, the ability to mount a vigorous IFN-gamma -response may play a role on the differential susceptibility to CCC development. (C) 2001 Academic Press.