Magalhães Luísa M D, Viana Agostinho, Chiari Egler, Galvão Lúcia M C, Gollob Kenneth J, Dutra Walderez O
Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Laboratório de Biologia do Trypanosoma cruzi e doença de Chagas, Departamento de Parasitologia, Instituto de Ciências Biológicas, Belo Horizonte, Minas Gerais, Brazil.
PLoS Negl Trop Dis. 2015 Jul 6;9(7):e0003816. doi: 10.1371/journal.pntd.0003816. eCollection 2015.
Trypanosoma cruzi strains are currently classified into six discrete typing units (DTUs) named TcI to VI. It is known that these DTUs have different geographical distribution, as well as biological features. TcI and TcII are major DTUs found in patients from northern and southern Latin America, respectively. Our hypothesis is that upon infection of human peripheral blood cells, Y strain (Tc II) and Col cl1.7 (Tc I), cause distinct immunological changes, which might influence the clinical course of Chagas disease.
METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the infectivity of CFSE-stained trypomastigotes of Col cl1.7 and Y strain in human monocytes for 15 and 72 hours, and determined the immunological profile of lymphocytes and monocytes exposed to the different isolates using multiparameter flow cytometry. Our results showed a similar percentage and intensity of monocyte infection by Y and Col cl1.7. We also observed an increased expression of CD80 and CD86 by monocytes infected with Col cl1.7, but not Y strain. IL-10 was significantly higher in monocytes infected with Col cl1.7, as compared to Y strain. Moreover, infection with Col cl1.7, but not Y strain, led to an increased expression of IL-17 by CD8+ T cells. On the other hand, we observed a positive correlation between the expression of TNF-alpha and granzyme A only after infection with Y strain.
CONCLUSION/SIGNIFICANCE: Our study shows that while Col cl1.7 induces higher monocyte activation and, at the same time, production of IL-10, infection with Y strain leads to a lower monocyte activation but higher inflammatory profile. These results show that TcI and TcII have a distinct immunological impact on human cells during early infection, which might influence disease progression.
克氏锥虫菌株目前被分为六个离散型单元（DTUs），命名为TcI至VI。已知这些DTUs具有不同的地理分布以及生物学特征。TcI和TcII分别是在拉丁美洲北部和南部患者中发现的主要DTUs。我们的假设是，人类外周血细胞感染Y株（Tc II）和Col cl1.7（Tc I）后会引起不同的免疫变化，这可能会影响恰加斯病的临床病程。
方法/主要发现：我们评估了CFSE标记的Col cl1.7和Y株锥鞭毛体在人单核细胞中15小时和72小时的感染性，并使用多参数流式细胞术确定了暴露于不同分离株的淋巴细胞和单核细胞的免疫谱。我们的结果显示，Y株和Col cl1.7感染单核细胞的百分比和强度相似。我们还观察到，感染Col cl1.7的单核细胞中CD80和CD86的表达增加，而Y株感染的单核细胞则没有。与Y株相比，感染Col cl1.7的单核细胞中IL-10显著更高。此外，感染Col cl1.7而非Y株会导致CD8 + T细胞中IL-17的表达增加。另一方面，我们仅在感染Y株后观察到TNF-α和颗粒酶A的表达之间存在正相关。
结论/意义：我们的研究表明，虽然Col cl1.7诱导更高的单核细胞活化，同时产生IL-10，但感染Y株会导致较低的单核细胞活化但更高的炎症谱。这些结果表明，TcI和TcII在早期感染期间对人类细胞具有不同的免疫影响，这可能会影响疾病进展。
