Table_3_Comparative Analysis of the Secretome and Interactome of Trypanosoma cruzi and Trypanosoma rangeli Reveals Species Specific Immune Response Modulating Proteins.XLSX

Chagas disease, a zoonosis caused by the flagellate protozoan Trypanosoma cruzi, is a chronic and systemic parasitic infection that affects ~5–7 million people worldwide, mainly in Latin America. Chagas disease is an emerging public health problem due to the lack of vaccines and effective treatments. According to recent studies, several T. cruzi secreted proteins interact with the human host during cell invasion. Moreover, some comparative studies with T. rangeli, which is non-pathogenic in humans, have been performed to identify proteins directly involved in the pathogenesis of the disease. In this study, we present an integrated analysis of canonical putative secreted proteins (PSPs) from both species. Additionally, we propose an interactome with human host and gene family clusters, and a phylogenetic inference of a selected protein. In total, we identified 322 exclusively PSPs in T. cruzi and 202 in T. rangeli. Among the PSPs identified in T. cruzi, we found several trans-sialidases, mucins, MASPs, proteins with phospholipase 2 domains (PLA2-like), and proteins with Hsp70 domains (Hsp70-like) which have been previously characterized and demonstrated to be related to T. cruzi virulence. PSPs found in T. rangeli were related to protozoan metabolism, specifically carboxylases and phosphatases. Furthermore, we also identified PSPs that may interact with the human immune system, including heat shock and MASP proteins, but in a lower number compared to T. cruzi. Interestingly, we describe a hypothetical hybrid interactome of PSPs which reveals that T. cruzi secreted molecules may be down-regulating IL-17 whilst T. rangeli may enhance the production of IL-15. These results will pave the way for a better understanding of the pathophysiology of Chagas disease and may ultimately lead to the identification of molecular targets, such as key PSPs, that could be used to minimize the health outcomes of Chagas disease by modulating the immune response triggered by T. cruzi infection.

美洲锥虫病，一种由鞭毛虫原生质体锥虫属克鲁斯氏虫（Trypanosoma cruzi）引起的动物源性疾病，是一种慢性且系统性的寄生虫感染，全球约有500万至700万人受到影响，主要分布于拉丁美洲地区。由于缺乏疫苗和有效的治疗方法，美洲锥虫病已成为一项新兴的公共卫生问题。根据近期的研究，多种T. cruzi分泌蛋白在细胞入侵过程中与人类宿主相互作用。此外，为了确定与疾病发病机制直接相关的蛋白，研究者们还进行了与对人无致病性的T. rangeli的比较研究。在本研究中，我们展示了两种物种中典型假定的分泌蛋白（PSPs）的集成分析。此外，我们提出了一个包含人类宿主和基因家族簇的相互作用网络，以及一个选定蛋白的进化推断。总计，我们在T. cruzi中鉴定出322种独特的PSPs，在T. rangeli中鉴定出202种。在T. cruzi中鉴定出的PSPs中，我们发现了一些转神经氨酶、粘蛋白、MASPs、具有磷脂酶2结构域（PLA2-like）的蛋白以及具有Hsp70结构域（Hsp70-like）的蛋白，这些蛋白先前已被特征化，并证实与T. cruzi的致病性相关。在T. rangeli中发现的PSPs与原生质体代谢相关，尤其是羧化酶和磷酸酶。此外，我们还鉴定出可能与人类免疫系统相互作用的PSPs，包括热休克和MASP蛋白，但数量较T. cruzi为少。有趣的是，我们描述了一个假想的PSPs混合相互作用网络，揭示了T. cruzi分泌的分子可能下调IL-17，而T. rangeli可能增强IL-15的产生。这些结果将为更深入理解美洲锥虫病的病理生理学奠定基础，并最终可能导致分子靶点的识别，例如关键的PSPs，这些靶点可以通过调节由T. cruzi感染触发的免疫反应来最小化美洲锥虫病的健康影响。