Human immunodeficiency virus-1 inhibition of immunoamphisomes in dendritic cells impairs early innate and adaptive immune responses.
Human immunodeficiency virus-1 inhibition of immunoamphisomes in dendritic cells impairs early innate and adaptive immune responses.
复制标题
DOI：
10.1016/j.immuni.2010.04.011
复制
发表时间：
2010-05-28
期刊：
影响因子：
32.4
通讯作者：
Piguet V
中科院分区：
文献类型：
--
作者：
Blanchet FP;Moris A;Nikolic DS;Lehmann M;Cardinaud S;Stalder R;Garcia E;Dinkins C;Leuba F;Wu L;Schwartz O;Deretic V;Piguet V
粘膜表面的树突状细胞（Dendritic cells，DC）是人类免疫缺陷病毒-1（human immunodeficiency virus-1，HIV-1）的早期靶细胞。在遇到病原体时，DC产生快速和强大的免疫应答。然而，在HIV-1传播的早期事件中的免疫应答似乎是有限的，这表明HIV-1逃避DC的早期免疫控制。我们报告说，HIV-1诱导DC中自噬和免疫两性体的快速关闭。HIV-1包膜激活了DC中的哺乳动物靶向雷帕霉素通路，导致自噬耗尽。HIV-1诱导的DC自噬抑制增加了细胞相关的HIV-1和HIV-1感染向CD 4 + T细胞的转移。HIV-1介导的DC自噬下调损害了先天性和适应性免疫应答。DC中的免疫两性体吞噬传入的病原体，并且似乎放大病原体降解以及Toll样受体应答和抗原呈递。HIV-1下调DCs的自噬并阻碍其免疫功能的发现代表了一种可以被解释为具有治疗和预防意义的发病机制。
Dendritic cells (DCs) in mucosal surfaces are early targets for human immunodeficiency virus-1 (HIV-1). DCs mount rapid and robust immune responses upon pathogen encounter. However, immune response in the early events of HIV-1 transmission appears limited, suggesting that HIV-1 evade early immune control by DCs. We report that HIV-1 induces a rapid shutdown of autophagy and immunoamphisomes in DCs. HIV-1 envelope activated the mammalian target of rapamycin pathway in DCs, leading to autophagy exhaustion. HIV-1-induced inhibition of autophagy in DC increased cell-associated HIV-1 and transfer of HIV-1 infection to CD4+ T cells. HIV-1-mediated downregulation of autophagy in DCs impaired innate and adaptive immune responses. Immunoamphisomes in DCs engulf incoming pathogens and appear to amplify pathogen degradation as well as Toll-like receptor responses and antigen presentation. The findings that HIV-1 downregulates autophagy and impedes immune functions of DCs represent a pathogenesis mechanism that can be pharmacologically countered with therapeutic and prophylactic implications.
登录
查看更多内容
影响因子：
4.5
作者：
Garcia, E;Pion, M;Piguet, V
通讯作者：
Piguet, V
影响因子：
5.4
作者：
Davenport, MP;Ribeiro, RM;Perelson, AS
通讯作者：
Perelson, AS
影响因子：
7.3
作者：
Guertin, David A.;Sabatini, David M.
通讯作者：
Sabatini, David M.
影响因子：
15.9
作者：
Espert, Lucile;Denizot, Melanie;Biard-Piechaczyk, Martine
通讯作者：
Biard-Piechaczyk, Martine
DOI：
10.1084/jem.194.8.1097
发表时间：
2001-10-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Castedo M;Ferri KF;Blanco J;Roumier T;Larochette N;Barretina J;Amendola A;Nardacci R;Métivier D;Este JA;Piacentini M;Kroemer G
通讯作者：
Kroemer G