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

The Toxoplasma gondii-Shuttling Function of Dendritic Cells Is Linked to the Parasite Genotype
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DOI:
10.1128/iai.01289-08
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发表时间:
2009-04-01
影响因子:
3.1
通讯作者:
Barragan, Antonio
Barragan, Antonio
中科院分区:
医学2区
文献类型:
--
作者:
Lambert, Henrik;Vutova, Polya P.;Barragan, Antonio

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肠道入侵后,导致专性细胞内原生动物弓形虫全身传播的过程仍然知之甚少。近年来,以Ⅰ、Ⅱ、Ⅲ型T.刚地虫种群显示出在它们穿越细胞屏障的能力方面不同。在这种主动寄生虫运动的过程中,I型菌株表现出比II型和III型菌株更上级的迁移能力。资料还表明,速殖子依赖于迁移的树突状细胞(DC)作为穿梭白细胞在组织中传播,如。例如,在一个实施例中,大脑,也就是囊肿形成的地方在本研究中,T.使从这三个群体中取样的弓形虫速殖子感染原代人血DC、鼠肠DC或体外衍生的DC,并比较不同的表型性状。T.在体外感染后不久,弓形虫在DC中诱导了超迁移表型。II型(和III型)菌株诱导更高的迁移频率和强度比I型菌株在DC。此外,在同基因小鼠中,受感染DC的过继转移有利于II型和III型寄生虫的传播,而不是I型寄生虫。与I型寄生虫相比,II型寄生虫在体内表现出与CD11c(+)DC和其他白细胞更强的细胞内结合。总之,这些研究结果表明,受感染的DC有助于寄生虫繁殖的菌株类型特异性的方式和寄生虫基因型(II型)最常见的弓形虫病在人类有效地利用DC迁移寄生虫传播。
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.