Protein S and Gas6 induce efferocytosis of HIV-1-infected cells.
Protein S and Gas6 induce efferocytosis of HIV-1-infected cells.
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DOI：
10.1016/j.virol.2017.12.025
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发表时间：
2018-03
期刊：
影响因子：
3.7
通讯作者：
Morizono K
中科院分区：
文献类型：
--
作者：
Chua BA;Ngo JA;Situ K;Ramirez CM;Nakano H;Morizono K
细胞吞噬作用，即对凋亡细胞的吞噬清除，通过调节感染细胞对正在发生凋亡的细胞的吞噬清除，提供宿主对某些类型病毒的保护。已知HIV-1可诱导细胞凋亡，巨噬细胞可吞噬HIV-1感染的细胞，但其分子机制尚不清楚。为了阐明HIV-1感染细胞的胞吐作用在清除感染细胞中所起的作用，我们试图确定介导这些过程的分子。我们发现，存在于人血清中的S蛋白及其同系物Gas6可以通过将表达在巨噬细胞上的受体酪氨酸激酶Mer连接到感染细胞上暴露的磷脂酰丝氨酸来介导HIV-1感染细胞的吞噬作用。活感染细胞的吞噬效率低于死亡感染细胞；然而，相当一部分活感染细胞在12h内被吞噬。我们的结果表明，吞噬作用不仅可以清除死亡细胞，还可能有助于巨噬细胞清除活的病毒产生细胞。
Efferocytosis, the phagocytic clearance of apoptotic cells, can provide host protection against certain types of viruses by mediating phagocytic clearance of infected cells undergoing apoptosis. It is known that HIV-1 induces apoptosis and HIV-1-infected cells are efferocytosed by macrophages, although its molecular mechanisms are unknown. To elucidate the roles that efferocytosis of HIV-1-infected cells play in clearance of infected cells, we sought to identify molecules that mediate these processes. We found that protein S, present in human serum, and its homologue, Gas6, can mediate phagocytosis of HIV-1-infected cells by bridging receptor tyrosine kinase Mer, expressed on macrophages, to phosphatidylserine exposed on infected cells. Efferocytosis of live infected cells was less efficient than dead infected cells; however, a significant fraction of live infected cells were phagocytosed over 12 h. Our results suggest that efferocytosis not only removes dead cells, but may also contribute to macrophage removal of live virus producing cells.
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