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S004 Trypanosoma cruzi interaction with host integrins and calcium channels stimulates microvesicle release to allow cell entry Ephraim A. Ansa-Addo and Jameel M. Inal London Metropolitan University, London, United Kingdom Chagas disease, the debilitating infection caused by the intracellular parasite, Trypanosoma cruzi, affects approximately 16 to 18 million individuals in Latin America and leads to about 50, 000 deaths per annum. Host microvesicles (MVs) help pathogens, such as the intracellular parasite, T. cruzi, evade complement attack. We have now found that the infectious metacyclic trypomastigote forms, by interacting with host integrins, lipid rafts and stretch activated channels, stimulate a calcium-mediated depolymerisation of the actin cytoskeleton, and MV release. The release of MVs in turn stimulates a lysosomal repair mechanism in the host cell, to plug the breach in the plasma membrane. By using specific inhibitors of lysosomal exocytosis and both pharmacological and siRNA-mediated inhibition of microvesicle release, we describe a novel entry mechanism by which the parasite opportunistically takes advantage of a host membrane repair mechanism, to execute entry before membrane integrity is fully restored. Our knowledge of this mechanism, and that its abrogation leads to reduced infection, is likely to lead to future potential therapies, for several increasingly important infectious diseases.