Mice with genetic deletion of group VIA phospholipase A2β exhibit impaired macrophage function and increased parasite load in Trypanosoma cruzi-induced myocarditis
Trypanosoma cruzi infection, which is the etiological agent of Chagas disease, is associated with intense inflammation during the acute and chronic phases. The pathological progression of Chagas disease is influenced by the infiltration and transmigration of inflammatory cells across the endothelium to infected tissues, which are carefully regulated processes involving several molecular mediators, including adhesion molecules and platelet-activating factor (PAF). We have shown that PAF production is dependent upon calcium-independent group VIA phospholipase A(2)β (iPLA(2)β) following infection of human coronary artery endothelial cells (HCAECs) with T. cruzi, suggesting that the absence of iPLA(2)β may decrease the recruitment of inflammatory cells to the heart to manage parasite accumulation. Cardiac endothelial cells isolated from iPLA(2)β-knockout (iPLA(2)β-KO) mice infected with T. cruzi demonstrated decreased PAF production compared to that by cells isolated from wild-type (WT) mice but demonstrated increases in adhesion molecule expression similar to those seen in WT mice. Myocardial inflammation in iPLA(2)β-KO mice infected with T. cruzi was similar in severity to that in WT mice, but the iPLA(2)β-KO mouse myocardium contained more parasite pseudocysts. Upon activation, macrophages from iPLA(2)β-KO mice produced significantly less nitric oxide (NO) and caused less T. cruzi inhibition than macrophages from wild-type mice. Thus, the absence of iPLA(2)β activity does not influence myocardial inflammation, but iPLA(2)β is essential for T. cruzi clearance
