Rapid cytoskeleton remodeling in dendritic cells following invasion by Toxoplasma gondii coincides with the onset of a hypermigratory phenotype
Weidner JM, Kanatani S, Hernández-Castañeda MA, Fuks JM, Rethi B, Wallin RP, Barragan A.
Center for Infectious Medicine, Department of Medicine, Tumor- and Cell Biology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Swedish Institute for Communicable Disease Control, Stockholm, Sweden.
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 up-regulation of C-C chemokine receptor 7 (CCR7). Yet, the onset of parasite-induced DC hypermotility preceded chemotactic migratory responses in 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.
PMID: 23534541 [PubMed - as supplied by publisher]
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