TY - JOUR
T1 - Antimicrobial peptide LL-37 produced by HSV-2-infected keratinocytes enhances hiv infection of langerhans cells
AU - Ogawa, Youichi
AU - Kawamura, Tatsuyoshi
AU - Matsuzawa, Takamitsu
AU - Aoki, Rui
AU - Gee, Peter
AU - Yamashita, Atsuya
AU - Moriishi, Kohji
AU - Yamasaki, Kenshi
AU - Koyanagi, Yoshio
AU - Blauvelt, Andrew
AU - Shimada, Shinji
N1 - Funding Information:
We would like to thank Kazutoshi Harada and Naotaka Shibagaki for their helpful discussions; Miyuki Ogino and Naoko Misawa for technical assistance; and Takashi Fujita, Keizo Tomonaga, and Klaus Strebel for providing reagents. These studies were supported in part by a grant from the Ministry of Education and Science of the Japanese Government. Y.O. performed experiments and analyzed data. T.K. directed and performed experiments, analyzed data, and wrote the manuscript. T.M. and R.A. performed experiments and analyzed data. P.G. and A.Y. performed experiments. K.M. contributed analytical tools. K.Y. and Y.K. codirected experiments. A.B. codirected experiments and wrote the manuscript. S.S. codirected experiments.
PY - 2013/1/16
Y1 - 2013/1/16
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84872572215&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2012.12.002
DO - 10.1016/j.chom.2012.12.002
M3 - Article
C2 - 23332157
AN - SCOPUS:84872572215
VL - 13
SP - 77
EP - 86
JO - Cell Host and Microbe
JF - Cell Host and Microbe
SN - 1931-3128
IS - 1
ER -
