Laboratório de Imunoparasitologia, Unidade de Pesquisa Integrada em Produtos Bioativos e Biociências, Universidade Federal do Rio de Janeiro, Macaé, Brazil.
Laboratório de Biologia Molecular de Parasitas e Vetores, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Front Cell Infect Microbiol. 2019 Apr 12;9:105. doi: 10.3389/fcimb.2019.00105. eCollection 2019.
amastigotes can make use of surface-exposed phosphatidylserine (PS) molecules to promote infection and non-classical activation of macrophages (MΦ), leading to uncontrolled intracellular proliferation of the parasites. This mechanism was quoted as apoptotic mimicry. Moreover, the amount of PS molecules exposed on the surface of amastigotes correlates with the susceptibility of the host. In this study, we tested whether host cellular responses influence PS expression on intracellular amastigotes. We found that the level of PS exposure on intracellular amastigotes was modulated by CD4 T cell and MΦ activation status and . infection generated a Th1/Th2-mixed cytokine profile, providing the optimal MΦ stimulation that favored PS exposure on intracellular amastigotes. Maintenance of PS exposed on the parasite was dependent on low, but sustained, levels of nitric oxide and polyamine production. Amastigotes obtained from lymphopenic nude mice did not expose PS on their surface, and adoptive transfer of CD4 T cells reversed this phenotype. In addition, histopathological analysis of mice treated with anti-PS antibodies showed increased inflammation and similarities to nude mouse lesions. Collectively, our data confirm the role of pathogenic CD4 T cells for disease progression and point to PS as a critical parasite strategy to subvert host immune responses.
无鞭毛体可以利用暴露在表面的磷脂酰丝氨酸（PS）分子促进感染和巨噬细胞（MΦ）的非经典激活，导致寄生虫的不受控制的细胞内增殖。这种机制被称为凋亡模拟。此外，无鞭毛体表面暴露的 PS 分子数量与宿主的易感性相关。在这项研究中，我们测试了宿主细胞反应是否会影响细胞内无鞭毛体上 PS 的表达。我们发现，CD4 T 细胞和 MΦ 激活状态调节细胞内无鞭毛体上 PS 的暴露水平，并且感染产生了 Th1/Th2 混合细胞因子谱，为有利于细胞内无鞭毛体上 PS 暴露的最佳 MΦ 刺激提供了条件。寄生虫表面 PS 的维持依赖于低但持续的一氧化氮和多胺产生水平。从淋巴缺失裸鼠中获得的无鞭毛体表面不暴露 PS，而 CD4 T 细胞的过继转移逆转了这种表型。此外，用抗 PS 抗体处理的小鼠的组织病理学分析显示炎症增加，与裸鼠病变相似。总的来说，我们的数据证实了致病性 CD4 T 细胞在疾病进展中的作用，并指出 PS 是寄生虫颠覆宿主免疫反应的关键策略。
