Transepithelial migration of Toxoplasma gondii involves an interaction of intercellular adhesion molecule 1 (ICAM-1) with the parasite adhesin MIC2
Transepithelial migration of Toxoplasma gondii involves an interaction of intercellular adhesion molecule 1 (ICAM-1) with the parasite adhesin MIC2
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DOI：
10.1111/j.1462-5822.2005.00486.x
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发表时间：
2005-04-01
影响因子：
3.4
通讯作者：
Sibley, LD
中科院分区：
文献类型：
--
作者：
Barragan, A;Brossier, F;Sibley, LD
弓形虫跨越肠道、血脑屏障和胎盘等不允许的生物屏障，从而接触到它最常导致严重病理的组织。在这里，我们表明，在迁移过程中，弓形虫最初集中在细胞间连接周围，并可能利用细胞旁途径跨越生物屏障进行迁移。寄生虫的转生需要活的和能动的寄生虫。有趣的是，寄主细胞屏障的完整性在寄生虫的迁徙过程中没有改变。随着细胞间黏附分子-1(ICAM-1)在弓形虫感染过程中在细胞屏障上表达上调，我们研究了该受体在寄生虫迁徙中的作用。可溶性的人ICAM-1和ICAM-1抗体可抑制寄生虫跨越细胞屏障的移行，涉及该受体在移行过程中的作用。此外，人ICAM-1免疫沉淀了寄生虫表面存在的成熟型粘附素MIC2，表明这种相互作用可能有助于细胞迁移。这些发现表明，弓形虫利用宿主内自然的细胞运输途径，跨越细胞屏障，传播到深层组织。
Toxoplasma gondii crosses non-permissive biological barriers such as the intestine, the blood-brain barrier and the placenta thereby gaining access to tissues where it most commonly causes severe pathology. Herein we show that in the process of migration Toxoplasma initially concentrates around intercellular junctions and probably uses a paracellular pathway to transmigrate across biological barriers. Parasite transmigration required viable and actively motile parasites. Interestingly, the integrity of host cell barriers was not altered during parasite transmigration. As intercellular adhesion molecule 1 (ICAM-1) is upregulated on cellular barriers during Toxoplasma infection, we investigated the role of this receptor in parasite transmigration. Soluble human ICAM-1 and ICAM-1 antibodies inhibited transmigration of parasites across cellular barriers implicating this receptor in the process of transmigration. Furthermore, human ICAM-1 immunoprecipitated the mature form of the parasite adhesin MIC2 present on the parasite surface, indicating that this interaction may contribute to cellular migration. These findings reveal that Toxoplasma exploits the natural cell trafficking pathways in the host to cross cellular barriers and disseminate to deep tissues.