Infect Immun. 2009 Feb 9. [Epub ahead of print]
The Toxoplasma gondii-Shuttling Function of Dendritic Cells is Linked to the Parasite Genotype
Lambert H, Vutova PP, Adams WC, Loré K, Barragan A.
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, SE-141 86 Stockholm, Sweden; Department of Parasitology, Mycology and Environmental Microbiology, and Department of Virology, Swedish Institute for Infectious Disease Control, SE-171 82 Stockholm, Sweden.
Following intestinal invasion, the processes leading to systemic dissemination of the obligate intracellular protozoan Toxoplasma gondii remain poorly understood. Recently, tachyzoites representative of type I, II and III T. gondii populations were shown to differ with respect to their ability to transmigrate across cellular barriers. In this process of active parasite motility, type I strains exhibit a superior migratory capacity than the type II and type III strains. Data also suggest that tachyzoites rely on migrating dendritic cells (DC) as shuttling leukocytes to disseminate in tissue, e.g. the brain where cysts develop. In this study, T. gondii tachyzoites sampled from the three populations were allowed to infect primary human blood DC, murine intestinal DC or in vitro-derived DC, and compared for different phenotypic traits. All three archetypical lineages of T. gondii induced a hypermigratory phenotype in DC shortly after infection in vitro. Type II (and III) strains induced higher migratory frequency and intensity in DC compared to type I. Additionally, adoptive transfer of infected DC favored dissemination of type II and type III parasites compared to type I parasites in syngeneic mice. Type II parasites exhibited stronger intracellular association to both CD11c(+) DC and other leukocytes in vivo compared to type I. Altogether, these findings suggest that infected DC contribute to parasite propagation in a strain type specific manner, and that the parasite genotype (type II) most frequently associated with toxoplasmosis in humans efficiently exploits DC migration for parasite dissemination.
PMID: 19204091 [PubMed - as supplied by publisher]