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

Research Project

Project/Area Number	21791067
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Dermatology
Research Institution	University of Yamanashi
Principal Investigator	OGAWA Youichi University of Yamanashi, 医学部附属病院, 助教 (20377542)
Project Period (FY)	2009 – 2010
Project Status	Completed (Fiscal Year 2010)
Budget Amount *help	¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2009: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords	皮膚感染症 / HIV / Langerhans cells / STDs / Toll-like receptors / APOBEC 3G / Lanerhans cells / Toll-like recetors
Research Abstract	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.