Aspirin Modulates Innate Inflammatory Response and Inhibits the Entry ofTrypanosoma cruziin Mouse Peritoneal Macrophages

Abstract

The intracellular protozoan parasiteTrypanosoma cruzicauses Chagas disease, a serious disorder that affects millions of people in Latin America. Cell invasion byT. cruziand its intracellular replication are essential to the parasite’s life cycle and for the development of Chagas disease. Here, we present evidence suggesting the involvement of the host’s cyclooxygenase (COX) enzyme duringT. cruziinvasion. Pharmacological antagonist for COX-1, aspirin (ASA), caused marked inhibition ofT. cruziinfection when peritoneal macrophages were pretreated with ASA for 30 min at 37°C before inoculation. This inhibition was associated with increased production of IL-1βand nitric oxide (NO∙) by macrophages. The treatment of macrophages with either NOS inhibitors or prostaglandin E2(PGE2) restored the invasive action ofT. cruziin macrophages previously treated with ASA. Lipoxin ALX-receptor antagonist Boc2 reversed the inhibitory effect of ASA on trypomastigote invasion. Our results indicate that PGE2,NO∙, and lipoxins are involved in the regulation of anti-T. cruziactivity by macrophages, providing a better understanding of the role of prostaglandins in innate inflammatory response toT. cruziinfection as well as adding a new perspective to specific immune interventions.