Malaria Sporozoites Traverse Host Cells within Transient Vacuoles
Malaria Sporozoites Traverse Host Cells within Transient Vacuoles
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DOI：
10.1016/j.chom.2015.10.006
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发表时间：
2015-11-11
影响因子：
30.3
通讯作者：
Silvie, Olivier
中科院分区：
文献类型：
--
作者：
Risco-Castillo, Veronica;Topcu, Selma;Silvie, Olivier
疟原虫子孢子通过按蚊沉积在宿主皮肤上。寄生虫从真皮迁移到肝脏，在那里它们通过移动结（MJ）侵入肝细胞，形成复制性寄生虫液泡（PV）。疟疾子孢子在通过宿主组织的过程中需要穿过细胞，这一过程需要寄生虫穿孔素样蛋白1（PLP1）。我们发现子孢子在PV形成之前穿过瞬时液泡内的细胞。子孢子最初通过主动的MJ独立过程侵入瞬时空泡内的细胞，该过程不需要空泡膜重塑或通常参与侵入的寄生虫分泌细胞器的释放。子孢子利用pH传感和PLP1离开这些空泡，避免被宿主溶酶体降解。接下来，寄生虫进入MJ依赖性PV，其具有不同的膜组成，排除了溶酶体融合。因此，疟原虫进化出不同的策略来逃避宿主细胞的防御，并建立一个细胞内的小生境进行复制。
Plasmodium sporozoites are deposited in the host skin by Anopheles mosquitoes. The parasites migrate from the dermis to the liver, where they invade hepatocytes through a moving junction (MJ) to form a replicative parasitophorous vacuole (PV). Malaria sporozoites need to traverse cells during progression through host tissues, a process requiring parasite perforin-like protein 1 (PLP1). We find that sporozoites traverse cells inside transient vacuoles that precede PV formation. Sporozoites initially invade cells inside transient vacuoles by an active MJ-independent process that does not require vacuole membrane remodeling or release of parasite secretory organelles typically involved in invasion. Sporozoites use pH sensing and PLP1 to exit these vacuoles and avoid degradation by host lysosomes. Next, parasites enter the MJ-dependent PV, which has a different membrane composition, precluding lysosome fusion. The malaria parasite has thus evolved different strategies to evade host cell defense and establish an intracellular niche for replication.