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巨噬细胞微管网络作为控制细胞内利什曼原虫命运的关键细胞控制器。

The macrophage microtubule network acts as a key cellular controller of the intracellular fate of Leishmania infantum.

机构信息

Université Paris-Saclay, CNRS, UMR 8076 BioCis, Châtenay-Malabry, France.

Université Paris-Saclay, Institut Paris-Saclay d'Innovation Thérapeutique (UMS-IPSIT), Unité Mixte de Services, Microscopy Facility, Châtenay-Malabry, France.

出版信息

PLoS Negl Trop Dis. 2020 Jul 28;14(7):e0008396. doi: 10.1371/journal.pntd.0008396. eCollection 2020 Jul.

DOI:10.1371/journal.pntd.0008396
PMID:32722702
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7386624/
Abstract

The parasitophorous vacuoles (PVs) that insulate Leishmania spp. in host macrophages are vacuolar compartments wherein promastigote forms differentiate into amastigote that are the replicative form of the parasite and are also more resistant to host responses. We revisited the biogenesis of tight-fitting PVs that insulate L. infantum in promastigote-infected macrophage-like RAW 264.7 cells by time-dependent confocal laser multidimensional imaging analysis. Pharmacological disassembly of the cellular microtubule network and silencing of the dynein gene led to an impaired interaction of L. infantum-containing phagosomes with late endosomes and lysosomes, resulting in the tight-fitting parasite-containing phagosomes never transforming into mature PVs. Analysis of the shape of the L. infantum parasite within PVs, showed that factors that impair promastigote-amastigote differentiation can also result in PVs whose maturation is arrested. These findings highlight the importance of the MT-dependent interaction of L. infantum-containing phagosomes with the host macrophage endolysosomal pathway to secure the intracellular fate of the parasite.

摘要

滋养液泡（PVs）将利什曼原虫与宿主巨噬细胞隔离，是一种隔离小泡，其中前鞭毛体形式分化为无鞭毛体，后者是寄生虫的复制形式，对宿主反应也更具抵抗力。我们通过时程共聚焦激光多维成像分析，重新研究了利什曼原虫在感染前鞭毛体的巨噬样 RAW 264.7 细胞中的紧密贴合 PV 的生物发生。细胞微管网络的药理学解体和动力蛋白基因沉默导致含有利什曼原虫的吞噬体与晚期内体和溶酶体的相互作用受损，导致紧密贴合的含有寄生虫的吞噬体从未转化为成熟的 PVs。对 PV 内利什曼原虫寄生虫形状的分析表明，破坏前鞭毛体-无鞭毛体分化的因素也可能导致 PV 成熟受阻。这些发现强调了 MT 依赖性利什曼原虫含吞噬体与宿主巨噬细胞内溶酶体途径相互作用，以确保寄生虫的细胞内命运的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/f600fdbcee5d/pntd.0008396.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/a6b0af5aa1d7/pntd.0008396.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/2c3af2ccb982/pntd.0008396.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/9a1c2435970c/pntd.0008396.g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/0f3212d6178a/pntd.0008396.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/46038bc839c1/pntd.0008396.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/1e013a5ca8a1/pntd.0008396.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/a756bbbfaac2/pntd.0008396.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/6241039f7884/pntd.0008396.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/f600fdbcee5d/pntd.0008396.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/a6b0af5aa1d7/pntd.0008396.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/2c3af2ccb982/pntd.0008396.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/9a1c2435970c/pntd.0008396.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/4b6c5845f1ce/pntd.0008396.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/0f3212d6178a/pntd.0008396.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/46038bc839c1/pntd.0008396.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/1e013a5ca8a1/pntd.0008396.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/a756bbbfaac2/pntd.0008396.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/6241039f7884/pntd.0008396.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbc0/7386624/f600fdbcee5d/pntd.0008396.g010.jpg

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