Cell Biology Unit, Institut Pasteur Montevideo, Montevideo, Uruguay.
Redox Biology of Trypanosomes Lab, Institut Pasteur de Montevideo, Montevideo, Uruguay.
Front Cell Infect Microbiol. 2023 Mar 9;13:1082524. doi: 10.3389/fcimb.2023.1082524. eCollection 2023.
Chagas disease (CD) is a life-threatening illness caused by the parasite (). With around seven million people infected worldwide and over 50,000 deaths per year, CD is a major public health issue in Latin America. The main route of transmission to humans is through a triatomine bug (vector-borne), but congenital and oral transmission have also been reported. The acute phase of CD presents mild symptoms but may develop into a long-lasting chronic illness, characterized by severely impaired cardiac, digestive, and neurological functions. The intestinal tissue appears to have a key role during oral transmission and chronic infection of CD. In this immune-privileged reservoir, dormant/quiescent parasites have been suggested to contribute to disease persistence, infection relapse, and treatment failure. However, the interaction between the intestinal epithelium and has not been examined in depth, in part, due to the lack of models that approximate to the biological and structural complexity of this tissue. Therefore, to understand the role played by the intestinal tissue during transmission and chronic infection, physiological models resembling the organ complexity are needed. Here we addressed this issue by establishing and characterizing adult stem cell-derived colonoid infection models that are clinically relevant for CD. 3D and 2D systems of murine intestinal organoids infected with Dm28c (a highly virulent strain associated with oral outbreaks) were analyzed at different time points by confocal microscopy. was able to invade and replicate in intestinal epithelial primary cells grown as intact organoids (3D) and monolayers (2D). The permissiveness to pathogen infection differed markedly between organoids and cell lines (primate and intestinal human cell lines). So far, this represents the first evidence of the potential that these cellular systems offer for the study of host-pathogen interactions and the discovery of effective anti-chagasic drugs.
恰加斯病（CD）是一种由寄生虫引起的危及生命的疾病（）。全球约有 700 万人感染，每年有超过 5 万人死亡，因此 CD 是拉丁美洲的一个主要公共卫生问题。人类感染的主要途径是通过一种原生动物（媒介传播），但也有先天性和口服传播的报道。CD 的急性阶段表现为轻微症状，但可能发展为持久的慢性疾病，其特征是心脏、消化和神经系统严重受损。肠道组织在 CD 的口服传播和慢性感染中似乎具有关键作用。在这个免疫特权储库中，休眠/静止寄生虫被认为有助于疾病持续存在、感染复发和治疗失败。然而，肠道上皮细胞与 之间的相互作用尚未得到深入研究，部分原因是缺乏接近该组织生物学和结构复杂性的 模型。因此，为了了解肠道组织在传播和慢性感染过程中所起的作用，需要建立类似于器官复杂性的生理模型。在这里，我们通过建立和表征与 CD 相关的成人干细胞衍生结肠类器官感染模型来解决这个问题。通过共聚焦显微镜分析了感染 Dm28c（一种与口服暴发相关的高毒力株）的 3D 和 2D 鼠肠类器官系统在不同时间点的情况。能够入侵和复制完整类器官（3D）和单层（2D）中生长的肠道上皮原代细胞。病原体感染的易感性在类器官和细胞系（灵长类和肠道人类细胞系）之间有显著差异。到目前为止，这是这些细胞系统在研究宿主-病原体相互作用和发现有效抗恰加斯病药物方面具有潜力的第一个证据。
