TSLP Production by Epithelial Cells Exposed to Immunodeficiency Virus Triggers DC-Mediated Mucosal Infection of CD4⁺ T Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 39; pp. 16776 - 16781
• Main Authors: Fontenot, Danielle, He, Hong, Hanabuchi, Shino, Nehete, Pramod N., Zhang, Minying, Chang, Mikyoung, Nehete, Bharti, Wang, Yui-Hsi, Wang, Yi-Hong, Ma, Zhong-min, Lee, Hai-Chon, Ziegler, Steven F., Courtney, Amy N., Milled, Christopher J., Sun, Shao-Cong, Liu, Yong-Jun, Sastry, K. Jagannadha, Steinman, Ralph M.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 29.09.2009; National Acad Sciences
• Subjects: Animals; Biological Sciences; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cells; Cells, Cultured; Coculture techniques; Cultured cells; Cytokines - biosynthesis; Dendritic Cells - metabolism; Disease transmission; Epithelial cells; Epithelial Cells - metabolism; Epithelial Cells - virology; Female; HIV; HIV 1; HIV-1 - pathogenicity; HIV-1 - physiology; Human immunodeficiency virus; Humans; Infections; Macaca mulatta; Messenger RNA; NF-kappa B - metabolism; Plasmids; Signal transduction; Simian Immunodeficiency Virus - pathogenicity; T cell receptors; T lymphocytes; Urogenital system; Viruses; Womens health
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0907347106

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 NFKB 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.