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Blood, 21 May 2009, Vol. 113, No. 21, pp. 5157-5166. Prepublished online as a Blood First Edition Paper on March 11, 2009; DOI 10.1182/blood-2008-10-185728. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-10-185728v1 113/21/5157    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ogawa, Y. Articles by Shimada, S. Search for Related Content PubMed PubMed Citation Articles by Ogawa, Y. Articles by Shimada, S. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Gram-positive bacteria enhance HIV-1 susceptibility in Langerhans cells, but not in dendritic cells, via Toll-like receptor activation Youichi Ogawa1, Tatsuyoshi Kawamura1, Tetsuya Kimura2, Masahiko Ito3, Andrew Blauvelt4, and Shinji Shimada1 1 Department of Dermatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan; 2 Department of Retrovirology and Self-Defense, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; 3 Department of Microbiology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan; and 4 Departments of Dermatology and Molecular Microbiology and Immunology, Oregon Health & Science University and Dermatology Service, Veterans Affairs Medical Center, Portland 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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