ROLE IN HOST-CELL INVASION OF TRYPANOSOMA-CRUZI-INDUCED CYTOSOLIC-FREE CA2+ TRANSIENTS

Trypanosoma cruzi enters cells by a unique mechanism, distinct from ph agocytosis. Invasion is facilitated by disruption of host cell actin m icrofilaments, and involves recruitment and fusion of host lysosomes a t the site of parasite entry. These findings implied the existence of transmembrane signaling mechanisms triggered by the parasites in the h ost cells before invasion. Here we show that infective trypomastigotes or their isolated membranes, but not the noninfective epimastigotes, induce repetitive cytosolic-free Ca2+ transients in individual normal rat kidney fibroblasts, in a pertussis toxin-sensitive manner. Parasit e entry is inhibited by buffering or depleting host cell cytosolic-fre e Ca2+, or by pretreatment with Ca2+ channel blockers or pertussis tox in. In contrast, invasion is enhanced by brief exposure of the host ce lls to cytochalasin D. These results indicate that a trypomastigote me mbrane factor triggers cytosolic-free Ca2+ transients in host cells th rough a G-protein-coupled pathway. This signaling event may promote in vasion through modulation of the host cell actin cytoskeleton.