Lambert Henrik, Vutova Polya P, Adams William C, Loré Karin, Barragan Antonio
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, SE-14186 Stockholm, Sweden.
Infect Immun. 2009 Apr;77(4):1679-88. doi: 10.1128/IAI.01289-08. Epub 2009 Feb 9.
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.
在肠道侵袭之后，导致专性细胞内原生动物刚地弓形虫全身播散的过程仍知之甚少。最近，代表I型、II型和III型弓形虫种群的速殖子在穿越细胞屏障的迁移能力方面表现出差异。在这种寄生虫主动运动的过程中，I型菌株的迁移能力优于II型和III型菌株。数据还表明，速殖子依靠迁移的树突状细胞（DC）作为穿梭白细胞在组织（如脑，囊肿在其中形成）中播散。在本研究中，从这三个种群中采集的弓形虫速殖子被用于感染原代人血DC、小鼠肠道DC或体外衍生的DC，并比较它们的不同表型特征。在体外感染后不久，弓形虫的所有三个典型谱系均在DC中诱导出高迁移表型。II型（和III型）菌株在DC中诱导的迁移频率和强度高于I型菌株。此外，在同基因小鼠中，感染DC的过继转移有利于II型和III型寄生虫的播散，而不是I型寄生虫。II型寄生虫在体内与CD11c(+) DC和其他白细胞的细胞内关联比I型寄生虫更强。总之，这些发现表明，受感染的DC以菌株类型特异性方式促进寄生虫繁殖，并且在人类中最常与弓形虫病相关的寄生虫基因型（II型）有效地利用DC迁移进行寄生虫播散。
