TSLP production by epithelial cells exposed to immunodeficiency virus triggers DC-mediated mucosal infection of CD4+ T cells.
Mucosal dendritic cells have been implicated in the capture, storage, and transmission of HIV to CD4(+) T cells as well as in the promotion of HIV replication in activated CD4(+) T cells during the cognate T-cell and DC interaction. We report that HIV induces human genital mucosal epithelial cells to produce thymic stromal lymphopoietin (TSLP) via activation of the NFkappaB signaling pathway. The TSLP secreted by HIV exposed epithelial cells activated DC, which promoted proliferation and HIV-1 replication of co-cultured autologous CD4(+) T cells. In rhesus macaques, we observed dramatic increases in TSLP expression concurrent with an increase in viral replication in the vaginal tissues within the first 2 weeks after vaginal SIV exposure. These data suggest that HIV-mediated TSLP production by mucosal epithelial cells is a critical trigger for DC-mediated amplification of HIV-infection in activated CD4(+) T cells. The cross talk between mucosal epithelial cells and DC, mediated by HIV-induced TSLP, may be an important mechanism for the high rate of HIV infection in women through the vaginal mucosa.
Fontenot
Danielle
D
Departments of Immunology and Veterinary Sciences, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, USA.
He
Hong
H
Hanabuchi
Shino
S
Nehete
Pramod N
PN
Zhang
Minying
M
Chang
Mikyoung
M
Nehete
Bharti
B
Wang
Yui-Hsi
YH
Wang
Yi-Hong
YH
Ma
Zhong-Min
ZM
Lee
Hai-Chon
HC
Ziegler
Steven F
SF
Courtney
Amy N
AN
Miller
Christopher J
CJ
Sun
Shao-Cong
SC
Liu
Yong-Jun
YJ
Sastry
K Jagannadha
KJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000821:virology*; D005260:Female; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008253:Macaca mulatta; D016328:NF-kappa B / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D016328:NF-kappa B; D000094632:Thymic Stromal Lymphopoietin