The inflammatory response in viral myocarditis: a quest for new targets and therapeutic strategies.

Viral myocarditis (VM) is an inflammatory pathology of the heart triggered by a viral infection. VM is characterised by variable and age-dependent symptoms: new-borns and young children are mostly affected by the acute form, whereas adult patients are affected by the chronic form. Although necessary for viral clearance, the host immune response is the primary cytotoxic agent in the cardiac tissue of VM patients. Excessive leukocyte stimulation leads to severe myocardial dysfunction, with an increased risk of chronic inflammation and dilated cardiomyopathy (DCM), and ultimately heart failure or sudden death. Current therapeutics focus on the symptoms, with no direct treatments available. In this project, we investigated the pathological progression of VM and identified potential key players in the regulation of the immune response. We used an in vivo Functional Selection (FunSel) technique to impartially screen cytokines involved in VM and investigated their role in inflammation during VM. Additionally, we investigated Stabilin-1, a scavenger receptor expressed in monocytes and macrophages, in the pathogenesis of VM. We demonstrated that stabilin-1 possesses an immune-suppressive function to limit cardiac necrosis and promote the recruitment of anti-inflammatory monocytes to the infected tissue. We also explored neutrophil and neutrophil extracellular trap (NET) role during VM. We proved that early inhibition of neutrophil functions reduces cardiac injury and inflammation and could represent a therapeutic approach to prevent pathological progression during acute phase of this pathology. Finally, we discussed the impact of these results and formulated new hypotheses and future research directions to strengthen our findings.