Uptake of apoptotic cells drives the growth of a pathogenic trypanosome inmacrophages

After apoptosis, phagocytes prevent inflammation and tissue damage by the u ptake and removal of dead cells(1). In addition, apoptotic cells evoke an a nti-inflammatory response through macrophages(2,3). We have previously show n that there is intense lymphocyte apoptosis in an experimental model of Ch agas' disease(4), a debilitating cardiac illness caused by the protozoan Tr ypanosoma cruzi. Here we show that the interaction of apoptotic, but not ne crotic T lymphocytes with macrophages infected with I: cruzi fuels parasite growth in a manner dependent on prostaglandins, transforming growth factor -beta (TGF-beta) and polyamine biosynthesis. We show that the vitronectin r eceptor is critical, in both apoptotic-cell cytoadherence and the induction of prostaglandin E-2/TGF-beta release and ornithine decarboxylase activity in macrophages. A single injection of apoptotic cells in infected mice inc reases parasitaemia, whereas treatment with cyclooxygenase inhibitors almos t completely ablates it in vivo. These results suggest that continual lymph ocyte apoptosis and phagocytosis of apoptotic cells by macrophages have a r ole in parasite persistence in the host, and that cyclooxygenase inhibitors have potential therapeutic application in the control of parasite replicat ion and spread in Chagas' disease.