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, tropical disease expert at Hull York Medical School.

'Transcriptomics of the immune response in Chagas heart disease'

Although the triggers for autoimmune disorders are diverse and, in many cases, unknown, some pathogens have the outstanding capacity to alter our immune system leading to malfunctioning and autoimmunity. Our laboratory is currently exploring the mechanisms that regulate infection-driven autoimmunity, particularly focusing on infection-driven heart disease. Cardiovascular diseases are the leading cause of death globally. The immune system plays a key role in cardiac development, composition, and function. Under some circumstances, particularly in response to infection, immune cells can infiltrate the heart in large numbers to remove dying tissue, scavenge pathogens and promote healing. If uncontrolled, these immune cells can cause collateral tissue damage, leading to heart dysfunction and failure. Moreover, the heart can be directly affected by autoreactive B cells, resulting in damage to its structures. 

Our goal is to better understand how the B cells that fight infections and those that attack the heart develop, and to identify the cellular and molecular mechanisms through which autoreactive B cells contribute to heart tissue damage. For this, we are using Trypanosoma cruzi as an infection model. T. cruzi is the protozoan parasite that causes Chagas disease (American trypanosomiasis), a major cause of infectious heart disease worldwide and the highest-impact parasitic disease in the Western Hemisphere. In response to T. cruzi infection/Chagas disease, and driven by poorly understood triggers, the immune system produces both antibodies against the parasite and against the body’s heart. Using a combination of molecular and cellular technologies (scRNA-seq, spatial transcriptomics, RNAScope, flow cytometry) we have now identified that chronic T. cruzi infection leads to a large and very unusual accumulation of B cells in the heart. During the talk, I will discuss our most recent datasets studying the immune response during experimental Chagas heart disease. I will also discuss our plans for studying the nature of these heart-resident B cells, how do they interact with other types of heart-resident cells (e.g. fibroblasts, cardiomyocytes) and ultimately, whether and how do they contribute to development of heart fibrosis and/or dilated cardiomyopathy.