Understanding autoimmunity: Why do B cells sometimes attack our tissues instead of protecting us from infections?

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B cells are white blood cells part of the body's immune system that produce antibodies and protect us from infections. On rare occasions, B cells produce antibodies that attack tissues leading to autoimmune diseases. Chagas disease, a neglected tropical disease caused by Trypanosoma cruzi parasites, is the leading cause of infectious heart disease worldwide and the highest-impact parasitic disease in the Western Hemisphere. In response to T. cruzi infection, the immune system produces two kinds of antibodies: 1) against the parasite (protective), 2) against the heart (harmful). How this happens is poorly understood. The goal of this Project is to discover the signals that drive the immune system to target the heart during T. cruzi infectionFor this, we have generated novel B-cell tetramers that allow us to isolate and study the molecular and functional characteristics of parasite- and heart-specific B cells. We also have access to a unique combination of:State-of-the-art facilities and multi-omics technologiesNovel mouse models of bioluminescent-reporter T. cruzi infectionsA bank of Chagas disease patient samplesWe will combine B-cell tetramers with flow cytometry, single-cell RNA sequencing, spatial transcriptomics, RNAscope, cutting-edge microscopy and recombinant antibodies to delineate molecular signatures, kinetics, tissue distribution and function of parasite- and heart-specific B cells in mice and humans. Running this study in both animal models and human samples will highly increase its translational value.Despite affecting more than the estimated number of people suffering from Parkinson's disease or lupus globally, Chagas disease receives little attention from governments. No vaccines are available and drug treatments are limited and toxic. This research will generate foundational knowledge that will help us produce novel treatments to improve life quality not only of people suffering this neglected tropical disease, but also autoimmune diseases in general.