Glycerol monolaurate prevents mucosal SIV transmission.
Glycerol monolaurate prevents mucosal SIV transmission.
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DOI：
10.1038/nature07831
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发表时间：
2009-04-23
期刊：
影响因子：
64.8
通讯作者：
Haase, Ashley T.
中科院分区：
文献类型：
--
作者：
Li, Qingsheng;Estes, Jacob D.;Schlievert, Patrick M.;Duan, Lijie;Brosnahan, Amanda J.;Southern, Peter J.;Reilly, Cavan S.;Peterson, Marnie L.;Schultz-Darken, Nancy;Brunner, Kevin G.;Nephew, Karla R.;Pambuccian, Stefan;Lifson, Jeffrey D.;Carlis, John V.;Haase, Ashley T.
虽然在治疗HIV-1感染方面取得了很大进展，但迄今为止，防止传播被证明是一个难以实现的目标。事实上，最近对一种候选疫苗和杀微生物剂的试验令人失望，既因为缺乏效力，也因为担心传播率增加。尽管如此，对siv -恒河猴模型阴道传播的研究指出，在感染的早期阶段，疫苗或杀微生物剂可能通过限制进入门户的受感染创始种群的扩大而起到保护作用。在这个siv -猕猴模型中，我们展示了一个由外而内的宫颈粘膜信号系统，包括MIP-3α、浆细胞样树突状细胞和由这些细胞产生的CCR5+细胞吸引趋化因子，结合子宫颈和阴道感染的先天免疫和炎症反应，招募CD4+T细胞来促进这种专性扩张。我们随后发现，单月牙酸甘油是一种广泛使用的抗菌化合物，具有抑制MIP-3α和其他促炎细胞因子产生的活性，在体外可以抑制粘膜信号传导以及对HIV-1和SIV的先天和炎症反应，在体内可以保护恒河猴免受急性感染，尽管阴道内反复暴露于高剂量SIV。这种新方法似乎与干扰先天性宿主反应有关，这些反应募集了建立全身感染所必需的靶细胞，为开发有效的干预措施来阻断HIV-1粘膜传播开辟了一条有希望的新途径。
While there has been great progress in treating HIV-1 infection, preventing transmission has thus far proven an elusive goal. Indeed, recent trials of a candidate vaccine and microbicide have been disappointing, both for want of efficacy and concerns about increased rates of transmission. Nonetheless, studies of vaginal transmission in the SIV-rhesus macaque model point to opportunities in the earliest stages of infection where a vaccine or microbicide might be protective, by limiting the expansion of infected founder populations at the portal of entry. Here we show in this SIV-macaque model, that an outside-in endocervical mucosal signalling system, involving MIP-3α, plasmacytoid dendritic cells and CCR5+cell-attracting chemokines produced by these cells, in combination with the innate immune and inflammatory responses to infection in both cervix and vagina, recruit CD4+T cells to fuel this obligate expansion. We then show that glycerol monolaurate, a widely used antimicrobial compound with inhibitory activity against production of MIP-3α and other proinflammatory cytokines, can inhibit mucosal signalling and the innate and inflammatory response to HIV-1 and SIV in vitro, and in vivo can protect rhesus macaques from acute infection despite repeated intra-vaginal exposure to high doses of SIV. This novel approach, plausibly linked to interfering with innate host responses that recruit the target cells necessary to establish systemic infection, opens a promising new avenue for development of effective interventions to block HIV-1 mucosal transmission.
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影响因子：
3.1
作者：
Peterson, ML;Ault, K;Schlievert, PM
通讯作者：
Schlievert, PM
影响因子：
5.4
作者：
Ma, ZM;Abel, K;Miller, CJ
通讯作者：
Miller, CJ
影响因子：
4.9
作者：
SCHLIEVERT, PM;DERINGER, JR;NOVICK, RP
通讯作者：
NOVICK, RP
影响因子：
2.9
作者：
Peterson, ML;Schlievert, PM
通讯作者：
Schlievert, PM
影响因子：
64.8
作者：
Li, QS;Duan, LJ;Haase, AT
通讯作者：
Haase, AT