Lysosomal fusion is essential for the retention of Trypanosoma cruzi inside host cells.
Lysosomal fusion is essential for the retention of Trypanosoma cruzi inside host cells.
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DOI：
10.1084/jem.20041408
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发表时间：
2004-11-01
影响因子：
15.3
通讯作者：
Andrews, NW
中科院分区：
文献类型：
--
作者：
Andrade, LO;Andrews, NW
锥鞭毛体是克氏锥虫的高度活动性感染形式，能够感染多种细胞类型。侵袭通过质膜处溶酶体的直接募集和融合而发生，或者通过质膜内陷然后与溶酶体在细胞内融合而发生。溶酶体样寄生液泡随后被破坏，释放寄生虫在细胞质中复制。克氏锥虫细胞内循环中溶酶体中的这种早期驻留的作用仍不清楚。对于其他几种胞质病原体，宿主细胞内的存活取决于在溶酶体融合之前早期逃离吞噬体。在这里，我们发现，当通过磷酸肌醇 3-激酶抑制来阻断溶酶体介导的克氏锥虫入侵时，很大一部分内化寄生虫随后不会保留在宿主细胞内进行有效感染。侵袭后溶酶体融合率与锥鞭毛体细胞内保留之间存在直接相关性。因此，具有溶酶体特性的寄生液泡的形成对于防止这些高度活动的寄生虫离开宿主细胞和完成细胞内生命周期至关重要。
Trypomastigotes, the highly motile infective forms of Trypanosoma cruzi, are capable of infecting several cell types. Invasion occurs either by direct recruitment and fusion of lysosomes at the plasma membrane, or through invagination of the plasma membrane followed by intracellular fusion with lysosomes. The lysosome-like parasitophorous vacuole is subsequently disrupted, releasing the parasites for replication in the cytosol. The role of this early residence within lysosomes in the intracellular cycle of T. cruzi has remained unclear. For several other cytosolic pathogens, survival inside host cells depends on an early escape from phagosomes before lysosomal fusion. Here, we show that when lysosome-mediated T. cruzi invasion is blocked through phosophoinositide 3-kinase inhibition, a significant fraction of the internalized parasites are not subsequently retained inside host cells for a productive infection. A direct correlation was observed between the lysosomal fusion rates after invasion and the intracellular retention of trypomastigotes. Thus, formation of a parasitophorous vacuole with lysosomal properties is essential for preventing these highly motile parasites from exiting host cells and for allowing completion of the intracellular life cycle.
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DOI：
10.1083/jcb.200201081
发表时间：
2002-03-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Glomski IJ;Gedde MM;Tsang AW;Swanson JA;Portnoy DA
通讯作者：
Portnoy DA
影响因子：
56.9
作者：
Tournier, C;Hess, P;Davis, RJ
通讯作者：
Davis, RJ
DOI：
10.4269/ajtmh.1975.24.25
发表时间：
1975-01-01
影响因子：
3.3
作者：
TANOWITZ, H;WITTNER, M;BLOOM, B
通讯作者：
BLOOM, B
DOI：
10.1084/jem.186.7.1159
发表时间：
1997-10-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Beauregard KE;Lee KD;Collier RJ;Swanson JA
通讯作者：
Swanson JA
影响因子：
11.4
作者：
HIGH, N;MOUNIER, J;SANSONETTI, PJ
通讯作者：
SANSONETTI, PJ