Authors

Discussion

Background

Chagas disease, caused by Trypanosoma cruzi parasites, is the most frequent cause of infectious cardiomyopathy in the world and the highest-impact parasitic disease in the Americas. No vaccines are available, and current medicines are toxic and limited. Historically a neglected tropical disease of the Americas, it is now spreading globally. Chagas heart disease (CHD) is an inflammatory cardiomyopathy that develops in approximately one-third of infected people. The reasons why some infected individuals develop cardiomyopathy while others remain asymptomatic for life remain largely unknown.  In response to T. cruzi infection, and driven by poorly understood triggers, the immune system produces both antibodies against the parasite and against the host’s heart tissues.

Methods

We used magnetic enrichment and novel B-cell tetramers combined with mouse models of bioluminescent T. cruzi infection to track, by flow cytometry and side-by-side, the development of T. cruzi-specific and cardiac-specific B-cell responses in spleen and heart.

Results

We observed a striking accumulation of plasma cell/plasmablast B cell subsets in the heart of T. cruzi-infected mice during early chronic infection. While T. cruzi-specific B cells gave rise to robust germinal centre responses in the spleen, cardiac-specific B-cell responses were primarily extrafollicular.

Conclusions

Our data suggest that activation of T. cruzi-specific and autoreactive cardiac-specific B cell responses are driven by drastically different mechanisms. Future work with our newly developed tools will allow us to identify the main drivers of pathogen vs autoreactive cardiac-specific B cell responses, as well as exploring the role of different B-cell subsets in the pathogenesis of CHD.