Upregulation of Cardiac IL-10 and Downregulation of IFN-γ in Balb/c IL-4-/- in Acute Chagasic Myocarditis due to Colombi Strain of Trypanosoma cruzi
Upregulation of Cardiac IL-10 and Downregulation of IFN-γ in Balb/c IL-4-/- in Acute Chagasic Myocarditis due to Colombi Strain of Trypanosoma cruzi
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DOI：
10.1155/2018/3421897
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发表时间：
2018-01-01
影响因子：
4.6
通讯作者：
Machado, Juliana Reis
中科院分区：
文献类型：
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作者：
da Silva, Marcos Vinicius;de Almeida, Vera Lucia;Machado, Juliana Reis
恰加斯病的炎症反应与寄生虫和宿主因素有关。然而，免疫系统的调节还没有完全阐明。因此，本研究旨在通过对感染的Balb/c WT和Balb/c IL-4(-/-)的心脏匀浆中细胞因子水平的影响及其组织病理学反应，来评价IL-4对克氏锥虫实验性感染急性期的影响。为此，小鼠被分成两组：感染组和未感染组，感染组有100种哥伦比亚菌株。感染21天后，动物被安乐死，并采集血液、脾和心脏。取脾细胞培养48h后，用LISA法检测血液、培养上清液和心尖部细胞因子TNF-α、IL-12p70、IL-10、干扰素-γ和IL-17的含量。取心脏底部作组织病理学分析。根据这些分析，与Balb/c WT相比，感染Balb/c IL-4(-/-)的小鼠表现出较轻的炎症浸润性，但巢密度和胶原沉积没有变化。IL-4的缺失最终导致心脏组织产生较低的干扰素-伽马，尽管它不影响原位的肿瘤坏死因子-α的表达。它还降低了全身和原位的肿瘤坏死因子-α的产生和IL-10的水平。此外，IL-4缺失不影响IL-17的表达。IL-4缺陷小鼠的脾细胞产生更多的干扰素-γ、肿瘤坏死因子-α和IL-17，而产生更少的IL-10。因此，在实验性感染克氏毛滴虫哥伦比亚株的急性期，IL-4的缺失减少了心肌炎，这是因为原位产生的干扰素-γ较低，而IL-10的产生较多，而且这种模式不受脾细胞总库的影响。
Inflammatory response in Chagas disease is related to parasite and host factors. However, immune system regulation has not been fully elucidated. Thus, this study is aimed at evaluating IL-4 influence on acute phase of Trypanosoma cruzi experimental infection through dosage of cytokine levels in cardiac homogenate of infected Balb/c WT and Balb/c IL-4(-/-) as well as its histopathological repercussions. For such purpose, mice were divided into two groups: an infected group with 100 forms of the Colombian strain and an uninfected group. After 21 days of infection, animals were euthanized and the blood, spleen, and heart were collected. The spleen was used to culture splenic cells in 48 h. Subsequently, cytolcines TNF-alpha, IL-12p70, IL-10, IFN-gamma, and IL-17 were measured in the blood, culture supernatant, and heart apex by [LISA. The base of the heart was used for histopathological analysis. From these analysis, infected Balb/c IL-4(-/-) mice showed milder inflammatory infiltrate compared to Balb/c WT, but without changes in nest density and collagen deposition. IL-4 absence culminated in lower cardiac tissue IFN-gamma production, although it did not affect TNF-alpha expression in situ. It also decreased TNF-alpha systemic production and increased IL-10, both systemically and in situ. In addition, IL-4 absence did not influence IL-17 expression. Splenocytes of IL-4-deficient mice produced higher amounts of IFN-gamma, TNF-alpha, and IL-17 and lower amounts of IL-10. Thus, IL-4 absence in acute phase of experimental infection with T. cruzi Colombian strain reduces myocarditis due to lower IFN-gamma production and greater IL-10 production in situ and this pattern is not influenced by splenocyte general repertoire.