Antimicrobial Peptide LL-37 Produced by HSV-2-Infected Keratinocytes Enhances HIV Infection of Langerhans Cells
Antimicrobial Peptide LL-37 Produced by HSV-2-Infected Keratinocytes Enhances HIV Infection of Langerhans Cells
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DOI：
10.1016/j.chom.2012.12.002
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发表时间：
2013-01-16
影响因子：
30.3
通讯作者：
Shimada, Shinji
中科院分区：
文献类型：
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作者：
Ogawa, Youichi;Kawamura, Tatsuyoshi;Shimada, Shinji
单纯疱疹病毒(HSV)-2的脱落与性感染艾滋病毒的风险增加有关。由于郎格汉斯细胞(LCS)是粘膜上皮树突状细胞，被怀疑是性行为后HIV感染的初始靶细胞之一，我们研究了HSV-2是否以及如何影响LCS的HIV感染。尽管检测到相对较少的HSV-2/HIV混合感染的LC，但HSV-2显著增加了皮肤组织中LC对HIV的敏感性。HSV-2刺激上皮细胞产生抗菌肽，包括人β防御素和LL-37。IL-37强烈上调单核细胞来源的LC的HIV受体的表达，从而增强其对HIV的敏感性。HSV-2感染的上皮细胞培养上清可增加MLCs对HIV的敏感性，这一作用可通过阻断IL-37的产生而被取消。这些数据表明，HSV-2通过产生IL-37上皮细胞增加LC对HIV的易感性，从而增强了HIV的性传播。
Herpes simplex virus (HSV)-2 shedding is associated with increased risk for sexually acquiring HIV. Because Langerhans cells (LCs), the mucosal epithelium resident dendritic cells, are suspected to be one of the initial target cell types infected by HIV following sexual exposure, we examined whether and how HSV-2 affects HIV infection of LCs. Although relatively few HSV-2/HIV-coinfected LCs were detected, HSV-2 dramatically enhanced the HIV susceptibility of LCs within skin explants. HSV-2 stimulated epithelial cell production of antimicrobial peptides (AMPs), including human beta defensins and LL-37. LL-37 strongly upregulated the expression of HIV receptors in monocyte-derived LCs (mLCs), thereby enhancing their HIV susceptibility. Culture supernatants of epithelial cells infected with HSV-2 enhanced HIV susceptibility in mLCs, and this effect was abrogated by blocking LL-37 production. These data suggest that HSV-2 enhances sexual transmission of HIV by increasing HIV susceptibility of LCs via epithelial cell production of LL-37.