Gram-positive bacteria enhance HIV-1 susceptibility in Langerhans cells, but not in dendritic cells, via Toll-like receptor activation
Gram-positive bacteria enhance HIV-1 susceptibility in Langerhans cells, but not in dendritic cells, via Toll-like receptor activation
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DOI：
10.1182/blood-2008-10-185728
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发表时间：
2009-05-21
期刊：
影响因子：
20.3
通讯作者：
Shimada, Shinji
中科院分区：
文献类型：
--
作者：
Ogawa, Youichi;Kawamura, Tatsuyoshi;Shimada, Shinji
虽然许多研究表明，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）被怀疑是性暴露后的初始HIV目标，我们研究了微生物成分是否通过激活Toll样受体（TLR）和核苷酸结合寡聚化结构域（NOD）模式识别受体来增强LC中的HIV感染。我们发现，TLR 1, 2和TLR 2/6激动剂显着增强了HIV易感性和复制在未成熟的单核细胞衍生的LC，而TLR 3 -5，TLR 7 -9，和NOD 1，2激动剂没有显着影响HIV感染。当LC与其他相关细菌组分以及与整个革兰氏（+）细菌一起孵育时，观察到相同的感染增强效应。在人类皮肤中的常驻LC中，TLR 2激动剂也显著增加了HIV易感性。相比之下，TLR 2激动剂和相关的细菌成分降低了单核细胞来源的树突状细胞（DC）中的HIV易感性。我们发现LC（而不是DC）的TLR 2激活导致APOBEC 3G显着下调，APOBEC 3G是HIV的细胞限制因子。鉴于这些数据，我们假设革兰氏（+）细菌产物连接TLR 2可能是伴随细菌性传播疾病感染发生的HIV性传播增强的基础。（血。2009; 113：5157-5166）
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 Toll-like receptor (TLR) and nucleotide-binding oligomerization domain (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, whereas TLR3-5, TLR7-9, and NOD1,2 agonists did not significantly affect HIV infection. 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. By contrast, TLR2 agonists and related bacterial components decreased HIV susceptibility in monocyte-derived dendritic cells (DCs). We found that TLR2 activation of LCs, but not DCs, 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. (Blood. 2009; 113: 5157-5166)