PGF2a levels in the TXA2 synthase null and WT mice were similar indicating this prostaglandin was likely not involved with the augmentation of parasitemia observed in the COX-1 null and ASA treated mice or in the regulation of mortality. This leaves the potential role of PGF2a in Chagas disease largely Regorafenib unexplored; however, the significant amounts of PGF2a produced by T. cruzi, and the fact that all members of the trypanosomatids have an identifiable synthase for PGF2a, indicate that it is of significant value to the parasite. During acute infection, PGE2 has been shown to modulate the virulence of the T. cruzi strain. A non-lethal strain provoked elevated circulating PGE2 while lethal strains did not. Inhibition of COX activity increased mortality in K98-strain infected mice but PGE2 infusion did not attenuate the virulence of the RA strain. Inhibition of PGE2 synthesis reduces both inflammatory infiltrates and cardiac fibrosis during acute infection. Conversely, preventing host response to parasite-derived TXA2 augmented death and parasitemia. TXA2 likely regulates vasospasm, thrombosis, vascular permeability and endothelial cell dysfunction during acute disease. TXA2 also displays immunosuppressive properties as WT mice display minimal pathology but TXA2 receptor null mice exhibited pronounced myocardial inflammation with an almost Paclitaxel 3-fold increased in parasite load in cardiac tissue. Thus, it appears that the eicosanoids present during acute infection largely act as immunomodulators that aid in the transition to and maintenance of the chronic phase of the disease. It is unclear whether T. cruzi generates prostaglandins as a defense against host immune system or whether it hijacks the host prostaglandin metabolic pathway in its favor. To this end, further studies using null mice missing biosynthetic enzymes or receptors are required to fully elucidate the role of the identified prostaglandins in Chagas disease. In contrast to acute infection, where plasma levels of multiple PGs are elevated, only increased levels of TXA2 are observed in chronic disease. In chronic disease the effects of TXA2 largely promote tissue damage, especially in the heart where it may exacerbate myocyte apoptosis and enhance progression to dilated cardiomyopathy and heart failure, a major cause of death in patients with this disease. Thus, disproving the adage that the things that don��t kill you make you stronger. In addition to the maelstrom of changes that TXA2 mediates during acute infection, the secretion of TXA2 would prevent the initiation of an adaptive immune response by the host, enabling progression to and maintenance of the chronic phase of the disease. Finally, the role for TXA2 in chronic disease is made more complicated by its control of parasite proliferation. While we have confirmed that TXA2 plays a prominent role in Chagas disease the hypothesis that parasitederived TXA2 is the primary quorum sensor for the parasite may need to be re-visited.