Sana Abel, Rossi Izadora Volpato, Sabatke Bruna, Ramirez Marcel Ivan
EVAHPI-Extracellular Vesicles and Host-Parasite Interactions Research Group, Laboratório de Biologia Celular, Instituto Carlos Chagas-Fiocruz, Curitiba 81350-010, Brazil.
Programa de Pós-Graduação em Biologia Celular e Molecular, Universidade Federal do Paraná (UFPR), Curitiba 80060-000, Brazil.
Life (Basel). 2025 Jun 9;15(6):931. doi: 10.3390/life15060931.
, the causative agent of Chagas disease, undergoes epimastigogenesis-a critical differentiation step in which trypomastigotes transform into epimastigotes. While this process is essential for the parasite's survival in its insect vector, the molecular mechanisms regulating it remain poorly understood. Here, we present the first evidence implicating extracellular vesicles (EVs) as enhancing mediators of epimastigogenesis. Using in vitro models with strains CL Brener and Dm28c, we demonstrate that EVs, membrane-bound vesicles, were shown to enhance differentiation in a strain-specific and temperature-dependent manner. We observed strain-specific EV release patterns: Dm28c produced more EVs at 24 h, whereas CL Brener peaked at 72 h. Additionally, we confirm that epimastigogenesis occurs exclusively at 28 °C after 72 h. These findings establish EVs as novel regulators of differentiation and suggest new insight into parasite development, highlighting potential targets for therapeutic intervention. The observed enhancement of differentiation in the presence of EVs indicates a potential role for these vesicles in this developmental process, although the underlying mechanisms remain undefined.
恰加斯病的病原体经历无鞭毛体生成——这是一个关键的分化步骤，在此过程中，锥鞭毛体转变为无鞭毛体。虽然这个过程对于寄生虫在其昆虫媒介中的生存至关重要，但调节它的分子机制仍知之甚少。在这里，我们提供了首个证据，表明细胞外囊泡（EVs）是无鞭毛体生成的增强介质。使用CL Brener和Dm28c菌株的体外模型，我们证明，膜结合囊泡EVs以菌株特异性和温度依赖性方式增强分化。我们观察到菌株特异性的EV释放模式：Dm28c在24小时产生更多的EVs，而CL Brener在72小时达到峰值。此外，我们证实无鞭毛体生成仅在72小时后于28°C发生。这些发现确立了EVs作为新型利什曼原虫分化调节剂的地位，并为寄生虫发育提供了新的见解，突出了治疗干预的潜在靶点。在EVs存在下观察到的分化增强表明这些囊泡在这个发育过程中具有潜在作用，尽管其潜在机制仍不明确。
