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Infection and Immunity, April 2009, p. 1679-1688, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01289-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Toxoplasma gondii-Shuttling Function of Dendritic Cells Is Linked to the Parasite Genotype{triangledown}

Henrik Lambert,1,2 Polya P. Vutova,1,2 William C. Adams,1,3 Karin Loré,1,3 and Antonio Barragan1,2*

Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, SE-141 86 Stockholm, Sweden,1 Department of Parasitology, Mycology and Environmental Microbiology,2 Department of Virology, Swedish Institute for Infectious Disease Control, SE-171 82 Stockholm, Sweden3

Received 21 October 2008/ Returned for modification 6 December 2008/ Accepted 2 February 2009

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 migratory capacity superior to those of 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 were 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 than type I strains did. Additionally, adoptive transfer of infected DC favored the dissemination of type II and type III parasites over that of type I parasites in syngeneic mice. Type II parasites exhibited stronger intracellular association with both CD11c+ DC and other leukocytes in vivo than did type I parasites. 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.

* Corresponding author. Mailing address: Swedish Institute for Infectious Disease Control, SE-171 82 Stockholm, Sweden. Phone: 46-8-4572524. Fax: 46-8-310525. E-mail: Antonio.Barragan{at}ki.se

{triangledown} Published ahead of print on 9 February 2009.

Editor: W. A. Petri, Jr.

Infection and Immunity, April 2009, p. 1679-1688, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01289-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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