Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, United States of America.
Laboratories of Molecular Anthropology and Microbiome Research, University of Oklahoma, Norman, Oklahoma, United States of America.
PLoS Negl Trop Dis. 2021 Oct 4;15(10):e0009819. doi: 10.1371/journal.pntd.0009819. eCollection 2021 Oct.
Chagas disease (CD), caused by the parasite Trypanosoma cruzi, is one of nineteen neglected tropical diseases. CD is a vector-borne disease transmitted by triatomines, but CD can also be transmitted through blood transfusions, organ transplants, T. cruzi-contaminated food and drinks, and congenital transmission. While endemic to the Americas, T. cruzi infects 7-8 million people worldwide and can induce severe cardiac symptoms including apical aneurysms, thromboembolisms and arrhythmias during the chronic stage of CD. However, these cardiac clinical manifestations and CD pathogenesis are not fully understood. Using spatial metabolomics (chemical cartography), we sought to understand the localized impact of chronic CD on the cardiac metabolome of mice infected with two divergent T. cruzi strains. Our data showed chemical differences in localized cardiac regions upon chronic T. cruzi infection, indicating that parasite infection changes the host metabolome at specific sites in chronic CD. These sites were distinct from the sites of highest parasite burden. In addition, we identified acylcarnitines and glycerophosphocholines as discriminatory chemical families within each heart region, comparing infected and uninfected samples. Overall, our study indicated global and positional metabolic differences common to infection with different T. cruzi strains and identified select infection-modulated pathways. These results provide further insight into CD pathogenesis and demonstrate the advantage of a systematic spatial perspective to understand infectious disease tropism.
恰加斯病（CD）由寄生虫克氏锥虫引起，是十九种被忽视的热带病之一。CD 是一种由三锥虫传播的虫媒病，但也可以通过输血、器官移植、受克氏锥虫污染的食物和饮料以及先天性传播。虽然在美洲流行，但全球有 700 至 800 万人感染克氏锥虫，在 CD 的慢性阶段可引起严重的心脏症状，包括心尖动脉瘤、血栓栓塞和心律失常。然而，这些心脏临床表现和 CD 的发病机制尚不完全清楚。使用空间代谢组学（化学制图），我们试图了解慢性 CD 对感染两种不同 T. cruzi 株的小鼠心脏代谢组的局部影响。我们的数据显示，慢性 T. cruzi 感染后局部心脏区域存在化学差异，这表明寄生虫感染会在慢性 CD 的特定部位改变宿主代谢组。这些部位与寄生虫负担最高的部位不同。此外，我们还确定了酰基辅酶 A 和甘油磷酸胆碱作为每个心脏区域中具有区分性的化学家族，比较感染和未感染的样本。总的来说，我们的研究表明，不同 T. cruzi 菌株感染的心脏存在普遍和位置代谢差异，并确定了一些感染调节的途径。这些结果进一步深入了解了 CD 的发病机制，并展示了系统的空间视角来理解传染病嗜性的优势。
