Antimicrobial peptide LL-37 produced by HSV-2-infected keratinocytes enhances hiv infection of langerhans cells

Youichi Ogawa, Tatsuyoshi Kawamura, Takamitsu Matsuzawa, Rui Aoki, Peter Gee, Atsuya Yamashita, Kohji Moriishi, Kenshi Yamasaki, Yoshio Koyanagi, Andrew Blauvelt, Shinji Shimada

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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 β 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.

Original languageEnglish
Pages (from-to)77-86
Number of pages10
JournalCell Host and Microbe
Volume13
Issue number1
DOIs
Publication statusPublished - 2013 Jan 16

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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    Ogawa, Y., Kawamura, T., Matsuzawa, T., Aoki, R., Gee, P., Yamashita, A., Moriishi, K., Yamasaki, K., Koyanagi, Y., Blauvelt, A., & Shimada, S. (2013). Antimicrobial peptide LL-37 produced by HSV-2-infected keratinocytes enhances hiv infection of langerhans cells. Cell Host and Microbe, 13(1), 77-86. https://doi.org/10.1016/j.chom.2012.12.002