title: Rapid cytoskeleton remodelling in dendritic cells following invasion by Toxoplasma gondii coincides with the onset of a hypermigratory phenotype.
abstract: Host cell manipulation is an important feature of the obligate intracellular parasite Toxoplasma gondii. Recent reports have shown that the tachyzoite stages subvert dendritic cells (DC) as a conduit for dissemination (Trojan horse) during acute infection. To examine the cellular basis of these processes, we performed a detailed analysis of the early events following tachyzoite invasion of human monocyte-derived DC. We demonstrate that within minutes after tachyzoite penetration, profound morphological changes take place in DC that coincide with a migratory activation. Active parasite invasion of DC led to cytoskeletal actin redistribution with loss of adhesive podosome structures and redistribution of integrins (CD18 and CD11c), that concurred with the onset of DC hypermotility in vitro. Inhibition of parasite rhoptry secretion and invasion, but not inhibition of parasite or host cell protein synthesis, abrogated the onset of morphological changes and hypermotility in DC dose-dependently. Also, infected DC, but not by-stander DC, exhibited upregulation of C-C chemokine receptor 7 (CCR7). Yet, the onset of parasite-induced DC hypermotility preceded chemotactic migratory responsesin vitro. Collectively, present data reveal that invasion of DC by T. gondii initiates a series of regulated events, including rapid cytoskeleton rearrangements, hypermotility and chemotaxis, that promote the migratory activation of DC.
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Swedish Institute for Communicable Disease Control, Stockholm, Sweden.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Weidner
authors.forename: Sachie
authors.initials: S
authors.lastname: Kanatani
authors.forename: Maria A
authors.initials: MA
authors.lastname: Hernández-Castañeda
authors.forename: Jonas M
authors.initials: JM
authors.lastname: Fuks
authors.forename: Bence
authors.initials: B
authors.lastname: Rethi
authors.forename: Robert P A
authors.initials: RP
authors.lastname: Wallin
authors.forename: Antonio
authors.initials: A
authors.lastname: Barragan
mesh_terms: D002465:Cell Movement; D002478:Cells, Cultured; D002633:Chemotaxis; D003599:Cytoskeleton / Q000378:metabolism*; D003713:Dendritic Cells / Q000469:parasitology* / Q000502:physiology*; D004705:Endocytosis; D054884:Host-Pathogen Interactions; D006801:Humans; D014122:Toxoplasma / Q000502:physiology*