title: Role in host cell invasion of Trypanosoma cruzi-induced cytosolic-free Ca2+ transients.
abstract: Trypanosoma cruzi enters cells by a unique mechanism, distinct from phagocytosis. Invasion is facilitated by disruption of host cell actin microfilaments, and involves recruitment and fusion of host lysosomes at the site of parasite entry. These findings implied the existence of transmembrane signaling mechanisms triggered by the parasites in the host 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. Parasite entry is inhibited by buffering or depleting host cell cytosolic-free Ca2+, or by pretreatment with Ca2+ channel blockers or pertussis toxin. In contrast, invasion is enhanced by brief exposure of the host cells to cytochalasin D. These results indicate that a trypomastigote membrane factor triggers cytosolic-free Ca2+ transients in host cells through a G-protein-coupled pathway. This signaling event may promote invasion through modulation of the host cell actin cytoskeleton.
authors.affiliation: Infectious Diseases Section, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: I
authors.initials: I
authors.lastname: Tardieux
authors.forename: M H
authors.initials: MH
authors.lastname: Nathanson
authors.forename: N W
authors.initials: NW
authors.lastname: Andrews
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000187:drug effects; D007668:Kidney / Q000469:parasitology; D007700:Kinetics; D037342:Pertussis Toxin; D051381:Rats; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000472:pathogenicity* / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D010566:Virulence Factors, Bordetella; D000001:Calcimycin; D037342:Pertussis Toxin; D002118:Calcium