The role of Toll-like receptor on sexual transmission of HIV

Toll样受体在HIV性传播中的作用

• 批准号: 21791067
• 负责人: OGAWA Youichi
• 金额: $ 2.83万
• 依托单位: University of Yamanashi
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21791067/
• 关键词: 皮膚感染症; HIV; Langerhans cells; STDs; Toll-like receptors; APOBEC 3G; Lanerhans cells; Toll-like recetors

Although numerous studies have shown a higher risk of acquiring HIV infection in the presence of other sexually transmitted diseases, the biologic mechanisms responsible for enhanced HIV acquisition are unclear. Because Langerhans cells (LCs) are suspected to be the initial HIV targets after sexual exposure, we studied whether microbial components augment HIV infection in LCs by activating TLR and NOD pattern recognition receptors. We found that TLR1/2 and TLR2/6 agonists dramatically enhanced both HIV susceptibility and replication in immature monocyte-derived LCs. The same infection-enhancing effects were observed when LCs were incubated with other related bacterial components as well as with whole Gram+ bacteria. In resident LCs in human skin, TLR2 agonists also significantly increased HIV susceptibility. We found that TLR2 activation of LCs, resulted in a significant down-regulation of APOBEC3G, which is a cellular restriction factor for HIV. Given these data, we hypothesize that ligation of TLR2 by Gram+ bacterial products may underlie enhanced sexual transmission of HIV that occurs with concomitant bacterial sexually transmitted disease infections.

尽管大量研究表明，在存在其他性传播疾病的情况下，感染艾滋病毒的风险更高，但导致艾滋病毒感染增加的生物学机制尚不清楚。由于朗格汉斯细胞 (LC) 被怀疑是性接触后最初的 HIV 目标，因此我们研究了微生物成分是否通过激活 TLR 和 NOD 模式识别受体来增强 LC 中的 HIV 感染。我们发现 TLR1/2 和 TLR2/6 激动剂显着增强了未成熟单核细胞来源的 LC 中的 HIV 易感性和复制。当 LC 与其他相关细菌成分以及整个革兰氏阳性细菌一起孵育时，观察到了相同的感染增强作用。在人体皮肤的常驻 LC 中，TLR2 激动剂也显着增加了 HIV 易感性。我们发现 TLR2 激活 LC 会导致 APOBEC3G 显着下调，APOBEC3G 是 HIV 的细胞限制因子。鉴于这些数据，我们假设革兰氏+细菌产物对TLR2的连接可能是伴随细菌性传播疾病感染而发生的HIV性传播增强的基础。

项目成果

Gram-positive bacteria enhance HIV-1 susceptibility in Langerhans cells, but not in dendritic cells, via Toll-like receptor activation

• DOI: 10.1182/blood-2008-10-185728
• 发表时间: 2009-05-21
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Ogawa, Youichi;Kawamura, Tatsuyoshi;Shimada, Shinji
• 通讯作者: Shimada, Shinji

Gram positive bacteria enhance HIV-1 susceptibility in Langerhans cells, but not in dendritic cells, via TLR activation

革兰氏阳性菌通过 TLR 激活增强郎格汉斯细胞中的 HIV-1 易感性，但不会增强树突状细胞中的 HIV-1 易感性

• 发表时间: 2009
• 期刊: Blood 113
• 作者: Furuichi M;Makino T;Yamakoshi T;Matsui K;Shimizu T;Youichi Ogawa
• 通讯作者: Youichi Ogawa