Reduction in adhesiveness to extracellular matrix components, modulation of adhesion molecules and in vivo migration of murine macrophages infected with Toxoplasma gondii
Reduction in adhesiveness to extracellular matrix components, modulation of adhesion molecules and in vivo migration of murine macrophages infected with Toxoplasma gondii
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DOI：
10.1016/j.micinf.2004.07.008
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发表时间：
2004-11-01
影响因子：
5.8
通讯作者：
Arnholdt, ACV
中科院分区：
文献类型：
--
作者：
Da Gama, LM;Ribeiro-Gomes, FL;Arnholdt, ACV
弓形虫是一种专性细胞内寄生虫，能够传播到深层组织并穿过生物屏障，到达免疫豁免部位，如大脑和视网膜。为探讨弓形虫是否利用白细胞运输在宿主体内传播，本文研究了RH株弓形虫感染小鼠后对细胞外基质成分的粘附能力、粘附分子的表达和体内迁移。弓形虫感染24 h后细胞与纤连蛋白、层粘连蛋白和IV型胶原的粘附力下降。然而，在早期感染时观察到的感染巨噬细胞粘附的减少在48 h后被逆转。而且。降低的粘附依赖于主动渗透，因为热杀死的寄生虫不能复制它。α 4和α 5链在感染后早期被下调，但在感染12小时后观察到表达的逐渐恢复。在晚期感染时，腹膜巨噬细胞的β 2、α v和α 4整合素表达也逐渐重建。与LPS预刺激的巨噬细胞相比，荧光染料5-氯甲基荧光素二乙酸酯标记的感染巨噬细胞体内迁移的评估显示迁移至颈部淋巴结延迟48小时。此外，迁移到远端淋巴结的细胞负载有活的寄生虫。总之，这些结果提供了有关弓形虫逃避宿主免疫反应的见解，将巨噬细胞作为“特洛伊木马”，有助于寄生虫传播和进入免疫豁免网站。(C)2004年，Elsevier SAS。All rights reserved.
Toxoplosma gondii is an obligate intracellular parasite, able to disseminate into deep tissues and cross biological barriers, reaching immunoprivileged sites such as the brain and retina. In order to investigate whether the parasite uses leukocyte trafficking to disseminate throughout the host, the adhesive potential to extracellular matrix components, the expression of adhesion molecules and the in vivo migration of murine rnacrophages infected with RH strain of T gondii were investigated. Cellular adhesion to fibronectin, laminin and collagen IV decreased after 24 h of T gondii infection. However, the decrease in adhesion of infected macrophages observed at early infection was reversed after 48 h. Moreover. decreased adhesion was dependent on active penetration, since heat-killed parasites were unable to reproduce it. Expression of integrins alphaL. alpha4 and alpha5 chains was downmodulated early postinfection, but a progressive regain of expression was observed after 12 h of infection. Expression of beta2, alphav and alpha4 integrins by peritoneal macrophages at late infection was also gradually reestablished. The assessment of in vivo migration of infected macrophages labeled with the fluorescent dye 5-chloromethylfluorescein diacetate showed a 48-h delay in migration to cervical lymph nodes when compared to LPS pre-stimulated macrophages. Furthermore, cells that migrate to distal lymph nodes were loaded with live parasites. Taken together, these results provide insights about T gondii escape from the host immune response, placing the macrophage as a "Trojan horse", contributing to parasite dissemination and access to immunoprivileged sites. (C) 2004 Elsevier SAS. All rights reserved.