Chagas´disease, caused by the protozoa Trypanosoma cruzi, is the major cause of cardiomyopathy in endemic areas of Latin America. Host resistance to T. cruzi infection depends on both innate and acquired immunity. Polymorphonuclear neutrophils (PMN) constitute the first line of defense against pathogens, however, they have been considered one of the major contributors to host damage in sub-acute and chronic inflammatory states. Migration of PMN from blood to tissues is a multi-step event dependent on lectin/sialylglycoproteins interactions mediating neutrophil-endothelial cell adhesion. T. cruzi expresses on its surface an inactive member of trans-sialidase family that physically interacts with sialic acid-containing molecules on host cells. Recently, we demonstrated that iTS binds to a2,3-linked sialic acid of CD43 (sialophorin) on humans neutrophils surface. In this work we investigated the role of iTS as a proinflammatory molecule, exploring iTS ability to activate neutrophil responses. iTS injection to the mouse air pouch resulted in a dose-dependent migration of neutrophils. In vitro, we demonstrated that iTS engagement to CD43 activates human neutrophils inducing actin cytoskeleton reorganization and synthesis of chemokine interleukin-8, pointing to a mechanism by which iTS induces chemotaxis in vivo. Incubation of human neutrophils with iTS triggered the production of reactive oxygen species as demonstrated by the oxidation of sodium borohydride-reduced derivative of ethidium bromide. In addition, we observed that iTS promotes activation of neutrophils through ERK-2 nuclear translocation and, delays PMN spontaneous apoptosis. Therefore, iTS is a pathogen-associated CD43 ligand, most likely involved in the inflammatory response during the acute phase of Chagas' disease.