Mice with genetic deletion of group VIA phospholipase A2β exhibit impaired macrophage function and increased parasite load in Trypanosoma cruzi-induced myocarditis

Janhavi Sharma, Jennifer R. Blase, Daniel F. Hoft, John O. Marentette, John Turk, Jane McHowat

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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 A2β (iPLA2β) following infection of human coronary artery endothelial cells (HCAECs) with T. cruzi, suggesting that the absence of iPLA2β may decrease the recruitment of inflammatory cells to the heart to manage parasite accumulation. Cardiac endothelial cells isolated from iPLA2β-knockout (iPLA2β-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 iPLA2β-KO mice infected with T. cruzi was similar in severity to that in WT mice, but the iPLA2β-KO mouse myocardium contained more parasite pseudocysts. Upon activation, macrophages from iPLA2β-KO mice produced significantly less nitric oxide (NO) and caused less T. cruzi inhibition than macrophages from wild-type mice. Thus, the absence of iPLA2β activity does not influence myocardial inflammation, but iPLA2β is essential for T. cruzi clearance.

Original languageEnglish
Pages (from-to)1137-1142
Number of pages6
JournalInfection and immunity
Volume84
Issue number4
DOIs
StatePublished - Apr 1 2016

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