Different infective forms trigger distinct immune response in experimental Chagas disease.

Different infective forms trigger distinct immune response in experimental Chagas disease.
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DOI:
10.1371/journal.pone.0032912
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Carneiro CM
Carneiro CM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Vieira PM;Francisco AF;Machado EM;Nogueira NC;Fonseca Kda S;Reis AB;Teixeira-Carvalho A;Martins-Filho OA;Tafuri WL;Carneiro CM

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虽然在寄生虫与宿主的相互作用和/或靶细胞入侵方面,元环和血锥乳鞭毛虫具有完全的功能,但它们表面存在的分子不同。因此,与克氏锥虫形式与宿主细胞相互作用的可变性相关的方面可能对针对这种寄生虫的免疫反应产生根本性影响,从而影响恰加斯病的临床演变。我们已经证明,BT感染的小鼠在感染的所有急性阶段呈现较高水平的寄生虫血症。此外,MT或BT感染均导致白细胞、单核细胞和淋巴细胞总量增加,MT较晚,BT较早。BT感染两种T细胞亚群产生促炎细胞因子TNF-α较早,产生IFN-γ较晚。这一事件伴随着早期心脏炎症,在急性期结束时这一过程加剧。另一方面,MT形式的感染导致IFN-γ的早期产生,随后由IL-10控制该细胞因子的产生,这为这些动物在急性期结束时提供了免疫调节特征。这些结果与心脏炎症的发现一致,感染MT形式的动物在感染后表现出强烈的心脏炎症,在该阶段结束时同样有所减少。总之,我们的研究结果强调了考虑克氏锥虫接种源的重要性,因为克氏锥虫感染的媒介或输血途径可能在急性期引发不同的寄生虫-宿主相互作用,这可能影响慢性恰加斯病的相关生物学方面。
Although metacyclic and blood trypomastigotes are completely functional in relation to parasite-host interaction and/or target cell invasion, they differ in the molecules present on the surface. Thus, aspects related to the variability that the forms of T. cruzi interacts with host cells may lead to fundamental implications on the immune response against this parasite and, consequently, the clinical evolution of Chagas disease. We have shown that BT infected mice presented higher levels of parasitemia during all the acute phase of infection. Moreover, the infection with either MT or BT forms resulted in increased levels of total leukocytes, monocytes and lymphocytes, specifically later for MT and earlier for BT. The infection with BT forms presented earlier production of proinflammatory cytokine TNF-α and later of IFN-γ by both T cells subpopulations. This event was accompanied by an early cardiac inflammation with an exacerbation of this process at the end of the acute phase. On the other hand, infection with MT forms result in an early production of IFN-γ, with subsequent control in the production of this cytokine by IL-10, which provided to these animals an immunomodulatory profile in the end of the acute phase. These results are in agreement with what was found for cardiac inflammation where animals infected with MT forms showed intense cardiac inflammation later at infection, with a decrease in the same at the end of this phase. In summary, our findings emphasize the importance of taking into account the inoculums source of T. cruzi, since vectorial or transfusional routes of T. cruzi infection may trigger distinct parasite-host interactions during the acute phase that may influence relevant biological aspects of chronic Chagas disease.
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