Cyclooxygenase-2 and Prostaglandin E₂ Signaling through Prostaglandin Receptor EP-2 Favor the Development of Myocarditis during Acute <i>Trypanosoma cruzi</i> Infection

<div><p>Inflammation plays an important role in the pathophysiology of Chagas disease, caused by <i>Trypanosoma cruzi</i>. Prostanoids are regulators of homeostasis and inflammation and are produced mainly by myeloid cells, being cyclooxygenases, COX-1 and COX-2, the key enzymes in their biosynthesis from arachidonic acid (AA). Here, we have investigated the expression of enzymes involved in AA metabolism during <i>T</i>. <i>cruzi</i> infection. Our results show an increase in the expression of several of these enzymes in acute <i>T</i>. <i>cruzi</i> infected heart. Interestingly, COX-2 was expressed by CD68⁺ myeloid heart-infiltrating cells. In addition, infiltrating myeloid CD11b⁺Ly6G^- cells purified from infected heart tissue express COX-2 and produce prostaglandin E₂ (PGE₂) <i>ex vivo</i>. <i>T</i>. <i>cruzi</i> infections in COX-2 or PGE₂-dependent prostaglandin receptor EP-2 deficient mice indicate that both, COX-2 and EP-2 signaling contribute significantly to the heart leukocyte infiltration and to the release of chemokines and inflammatory cytokines in the heart of <i>T</i>. <i>cruzi</i> infected mice. In conclusion, COX-2 plays a detrimental role in acute Chagas disease myocarditis and points to COX-2 as a potential target for immune intervention.</p>