Meeting the Challenges of Myocarditis: New Opportunities for Prevention, Detection, and Intervention—A Report from the 2021 National Heart, Lung, and Blood Institute Workshop

Figures

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  Figure 1. T helper cell pathways leading to three subtypes of myocarditis. Viral myocarditis activating Th1 pathway driven by IL-12 induces IFNγ production and CD8+ T cells as the main effector cells. Hypersensitivity myocarditis is induced by Th2 pathway driven by cytokines (IL-4, IL5, and IL13), mast cells, eosinophils, and B cells. Autoimmune myocarditis is driven by the Th17 pathway, with the IL17A/ F, and GM-CSF as the main cytokines inducing neutrophil and inflammatory monocyte responses.

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  Figure 2. Experimental autoimmune myocarditis murine model. In the EAM model, cardiac myosin or the relevant peptide in Freund’s complete adjuvant is injected subcutaneously into mice on day 0 and day 7. The immune response, the histological changes, and the genetic susceptibility observed in EAM are similar to giant cell myocarditis. #: The numbers are identifying the epitope of myosin heavy chain (MYHC) used for the induction of myocarditis.

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  Figure 3. Immune regulation of coxsackievirus B3-induced myocarditis. Coxsackievirus B3 has the ability to infect cardiomyocytes. The innate immune system including ILCs, NK cells, macrophages, and dendritic cells in the heart is activated after the release of damage-associated molecular patterns (DAMPs). Cardiac stroma cells such as fibroblasts are also activated. Together with the immune cells, they release chemokines and cytokines that attract other immune cells from circulation. In addition, bone marrow is activated and increases hematopoiesis by the heart-derived mediators such as IL-1β, GM-CSF, and DAMPs. The gut is a possible other source of inflammatory cells such as Th17 cells that could have been primed by gut microbiota.