Uptake of apoptotic cells drives the growth of a pathogenic trypanosome in macrophages

After apoptosis, phagocytes prevent inflammation and tissue damage by the uptake and removal of dead cells 1 . In addition, apoptotic cells evoke an anti-inflammatory response through macrophages 2 , 3 . We have previously shown that there is intense lymphocyte apoptosis in an experimental model of Chagas' disease 4 , a debilitating cardiac illness caused by the protozoan Trypanosoma cruzi . Here we show that the interaction of apoptotic, but not necrotic T lymphocytes with macrophages infected with T. cruzi fuels parasite growth in a manner dependent on prostaglandins, transforming growth factor-β (TGF-β) and polyamine biosynthesis. We show that the vitronectin receptor is critical, in both apoptotic-cell cytoadherence and the induction of prostaglandin E 2 /TGF-β release and ornithine decarboxylase activity in macrophages. A single injection of apoptotic cells in infected mice increases parasitaemia, whereas treatment with cyclooxygenase inhibitors almost completely ablates it in vivo . These results suggest that continual lymphocyte apoptosis and phagocytosis of apoptotic cells by macrophages have a role in parasite persistence in the host, and that cyclooxygenase inhibitors have potential therapeutic application in the control of parasite replication and spread in Chagas' disease.