TSLP production by epithelial cells exposed to immunodeficiency virus triggers DC-mediated mucosal infection of CD4+ T cells

Danielle Fontenot, Hong He, Shino Hanabuchi, Pramod N. Nehete, Minying Zhang, Mikyoung Chang, Bharti Nehete, Yui Hsi Wang, Yi Hong Wang, Zhong Min Ma, Hai Chon Lee, Steven F. Ziegler, Amy N. Courtney, Chris J Miller, Shao Cong Sun, Yong Jun Liu, K. Jagannadha Sastry

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

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 NFκB 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.

Original languageEnglish (US)
Pages (from-to)16776-16781
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number39
DOIs
StatePublished - Sep 29 2009

Keywords

  • Dendritic cells
  • HIV

ASJC Scopus subject areas

  • General

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    Fontenot, D., He, H., Hanabuchi, S., Nehete, P. N., Zhang, M., Chang, M., Nehete, B., Wang, Y. H., Wang, Y. H., Ma, Z. M., Lee, H. C., Ziegler, S. F., Courtney, A. N., Miller, C. J., Sun, S. C., Liu, Y. J., & Jagannadha Sastry, K. (2009). TSLP production by epithelial cells exposed to immunodeficiency virus triggers DC-mediated mucosal infection of CD4+ T cells. Proceedings of the National Academy of Sciences of the United States of America, 106(39), 16776-16781. https://doi.org/10.1073/pnas.0907347106