Departamento de Morfologia, Laboratório de Biologia das Interações Celulares, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Departamento de Parasitologia, Laboratório de Biologia do Trypanosoma cruzi e doença de Chagas, Instituto de Ciências Biológicas, Belo Horizonte, Brazil.
Parasite Immunol. 2019 Nov;41(11):e12668. doi: 10.1111/pim.12668. Epub 2019 Sep 30.
The aim of the study was to evaluate the immune response triggered by the first contact of human monocytes with two T cruzi strains from distinct discrete typing units (DTUs) IV and V, and whether co-infection with these strains leads to changes in monocyte immune profiles, which could in turn influence the subsequent infection outcome.
We evaluated the influence of in vitro single- and co-infection with AM64 and 3253 strains on immunological characteristics of human monocytes. Single infection of monocytes with AM64 or 3253 induced opposing anti-inflammatory and inflammatory responses, respectively. Co-infection was observed in over 50% of monocytes after 15 hours of culture, but this percentage dropped ten-fold after 72 hours. Co-infection led to high monocyte activation and an increased percentage of both IL-10 and TNF. The decreased percentage of co-infected cells observed after 72 hours was associated with a decreased frequency of TNF-expressing cells.
Our results show that the exacerbated response observed in co-infection with immune-polarizing strains is associated with a decreased frequency of co-infected cells, suggesting that the activated response favours parasite control. These findings may have implications for designing new Chagas disease preventive strategies.
本研究旨在评估人类单核细胞与来自不同离散型单位(DTU)IV 和 V 的两种 T 克鲁兹锥虫株首次接触所引发的免疫反应,以及这两种虫株的合并感染是否会导致单核细胞免疫谱的变化,进而影响后续的感染结果。
我们评估了 AM64 和 3253 株的体外单感染和合并感染对人单核细胞免疫特性的影响。单核细胞单独感染 AM64 或 3253 株分别诱导出相反的抗炎和促炎反应。在培养 15 小时后,超过 50%的单核细胞观察到合并感染,但在 72 小时后,这一比例下降了十倍。合并感染导致单核细胞高度激活,并增加了 IL-10 和 TNF 的比例。72 小时后观察到合并感染细胞比例下降与 TNF 表达细胞频率下降有关。
我们的结果表明,与免疫极化株合并感染时观察到的过度反应与合并感染细胞的频率降低有关,提示激活的反应有利于寄生虫的控制。这些发现可能对设计新的恰加斯病预防策略具有重要意义。