Exosomal Hsp70 induces a pro-inflammatory response to foreign particles including mycobacteria.
Exosomal Hsp70 induces a pro-inflammatory response to foreign particles including mycobacteria.
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DOI：
10.1371/journal.pone.0010136
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发表时间：
2010-04-12
期刊：
影响因子：
3.7
通讯作者：
Griffiths G
中科院分区：
文献类型：
--
作者：
Anand PK;Anand E;Bleck CK;Anes E;Griffiths G
外泌体是内体衍生的囊泡，当多囊泡体（MVB）与质膜融合时释放。从分枝杆菌感染的细胞释放的外来体最近已被证明是促炎性的。在这些外泌体中发现的一个突出的宿主分子是Hsp 70，它是热休克蛋白家族的成员。我们首先表征了从对照和分枝杆菌感染的细胞中纯化的外泌体。我们发现，相对于未感染的细胞，M. smegalgae和M.鸟类释放更多的外泌体，并且它们释放的外泌体在其表面上具有更多的Hsp 70。巨噬细胞的外泌体和外源性Hsp 70处理均导致未感染巨噬细胞中NF-κB活化和TNFα释放;在分枝杆菌感染的细胞中Hsp 70水平升高。用Hsp 70处理巨噬细胞也导致胶乳珠吞噬体的吞噬作用和成熟的增加。最后，将M. smega-and M.禽流感感染的细胞导致吞噬-溶酶体融合增加，以及对巨噬细胞内分枝杆菌的更多杀伤。我们的研究结果符合一个新兴的概念，即含有外泌体的Hsp 70是炎症的有效诱导剂，也是对分枝杆菌感染的反应。
Exosomes are endosome-derived vesicles that are released when multi-vesicular bodies (MVBs) fuse with the plasma membrane. Exosomes released from mycobacteria-infected cells have recently been shown to be pro-inflammatory. A prominent host molecule that is found within these exosomes is Hsp70, a member of the heat-shock family of proteins. We first characterized the exosomes purified from control and mycobacteria-infected cells. We found that relative to uninfected cells, macrophages infected with M. smegmatis and M. avium release more exosomes and the exosomes they released had more Hsp70 on their surface. Both exosomes and exogenous Hsp70 treatment of macrophages led to NF-κB activation and TNFα release in uninfected macrophages; Hsp70 levels were elevated in mycobacteria-infected cells. Macrophage treatment with Hsp70 also led to increase in the phagocytosis and maturation of latex-bead phagosomes. Finally, Hsp70 pre-incubation of M. smegmatis- and M. avium-infected cells led to increased phago-lysosome fusion, as well as more killing of mycobacteria within macrophages. Our results fit into an emerging concept whereby exosomes-containing Hsp70 are effective inducers of inflammation, also in response to mycobacterial infection.
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