Dual role of signaling pathways leading to Ca2+ and cyclic AMP elevation in host cell invasion by Trypanosoma cruzi
Dual role of signaling pathways leading to Ca2+ and cyclic AMP elevation in host cell invasion by Trypanosoma cruzi
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DOI：
10.1128/iai.68.12.6602-6610.2000
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发表时间：
2000-12-01
影响因子：
3.1
通讯作者：
Andrews, NW
中科院分区：
文献类型：
--
作者：
Caler, EV;Morty, RE;Andrews, NW
原生动物寄生虫克氏锥虫的细胞入侵涉及宿主信号通路的激活以及寄生虫进入位点的溶酶体的募集和融合。调节成纤维细胞、上皮细胞和成肌细胞侵袭的主要信号通路涉及从细胞内储存的Ca 2+的动员，并且需要T. cruzi丝氨酸肽酶，寡肽酶B（OP B）。OPE基因的缺失导致锥鞭毛体毒力的显著缺陷，与细胞侵袭能力的大大降低一致。在这里，我们表明，由巨噬细胞的摄取，另一方面，在很大程度上是独立的OPE表达和细胞松弛素D的抑制敏感，在成纤维细胞中的OPB空锥鞭毛体的残余侵入能力仍然涉及溶酶体招聘，虽然在一个显着延迟的方式。在暴露于野生型和OPB空锥鞭毛体的宿主细胞中观察到细胞内Ca2+浓度的瞬时升高，但突变体寄生虫触发的信号不那么强烈和延迟。然而，在OPB无效的锥鞭毛体中，触发宿主细胞环AMP（cAMP）升高的能力没有改变。cAMP水平的调节优先影响OPB无效寄生虫的残余细胞侵袭能力，这表明该信号传导途径可以在主要OPB依赖性途径不存在的情况下在促进细胞侵袭中发挥主导作用。
Cell invasion by the protozoan parasite Trypanosoma cruzi involves activation of host signaling pathways and the recruitment and fusion of lysosomes at the parasite entry site. A major signaling pathway regulating invasion of fibroblasts, epithelial cells, and myoblasts involves mobilization of Ca2+ from intracellular stores and requires the activity of a T. cruzi serine peptidase, oligopeptidase B (OPB). Deletion of the OPE gene results in a marked defect in trypomastigote virulence, consistent with a greatly reduced cell invasion capacity. Here we show that uptake by macrophages, on the other hand, is largely independent of OPE expression and sensitive to inhibition of by cytochalasin D, The residual invasion capacity of OPBnull trypomastigotes in fibroblasts still involves lysosome recruitment, although in a significantly delayed fashion. Transient elevations in intracellular Ca2+ concentrations were observed in host cells exposed to both wild-type and OPBnull trypomastigotes, but the signals triggered by the mutant parasites were less vigorous and delayed. The capacity of triggering elevation in host cell cyclic AMP (cAMP), however, was unaltered in OPBnull trypomastigotes. Modulation in cAMP levels preferentially affected the residual cell invasion capacity of OPBnull parasites, suggesting that this signaling pathway can play a dominant role in promoting cell invasion in the absence of the major OPB dependent pathway.