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RESEARCH PRODUCT

Does Autoimmunity Play a Role in the Immunopathogenesis of Vasculitis Associated With Chronic Chagas Disease?

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Chagas disease (CD) is a chronic systemic vector-borne infection caused by the protozoan Trypanosoma cruzi. It has spread from Latin America through migration, becoming a global issue (Perez-Molina and Molina, 2018). Its prevalence is ∼7 million people worldwide, of whom 30-40% will develop severe chronic complications such as cardiomyopathy or megaviscerae, with a considerable impact on morbimortality (WHO, 2020; WHO, 2021). The parasite is transmitted after metacyclic trypomastigotes in the feces of a triatomine insect enter the host through the bite wound. They penetrate cells and transform into amastigotes, where they multiply by binary fission and differentiate again into circulating trypomastigotes after rupture of the host cell. The triatomine vector ingests them from an infected individual and they replicate in its intestine in the form of epimastigotes. The cycle closes after the epimastigotes differentiate again into metacyclic trypomastigotes (Perez-Molina and Molina, 2018). Chronic clinical manifestations in CD have been associated with a disproportionate inflammation compared to the parasitic burden (Cunha-Neto et al., 2011), driven by direct parasitic invasiveness (Bonney and Engman, 2008; Epting et al., 2010), damage to bystander cells (De Bona et al., 2018), cellular injury due to non-specific immune responses (Bellotti et al., 1996; Zhang and Tarleton, 1999; Bonney and Engman, 2015; De Bona et al., 2018), autoimmunity (Leon et al., 2001; Engman and Leon, 2002; Bonney and Engman, 2015; De Bona et al., 2018), and vasculitis (Roffe et al., 2016; Weaver et al., 2019). Herein, we review the autoimmune mechanisms behind chronic CD and, particularly, the knowledge gaps in the immunopathogenesis of vasculitis developed in patients with CD.