1. Defective Plasmacytoid Dendritic Cell-NK Cell Cross-Talk in HIV Infection
- Author
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Xiao Zhang, Richard A. Lempicki, J. Arthos, Claire W. Hallahan, Anthony S. Fauci, M. Yan, Gregg Roby, Kristin N. Reitano, M.A. O'Shea, J. Yang, Shyam Kottilil, and C.M. Gille
- Subjects
Integrins ,Immunology ,HIV Infections ,Viremia ,Plasmacytoid dendritic cell ,HIV Envelope Protein gp120 ,Biology ,Natural killer cell ,Interleukin 21 ,Immune system ,Virology ,medicine ,Humans ,Innate immune system ,Tumor Necrosis Factor-alpha ,Interferon-alpha ,virus diseases ,Dendritic Cells ,Dendritic cell ,medicine.disease ,Killer Cells, Natural ,Infectious Diseases ,medicine.anatomical_structure ,Tumor necrosis factor alpha ,Protein Binding - Abstract
HIV viremia is associated with a wide range of immune dysfunctions that contribute to the immunocompromised state. HIV viremia has been shown to have a broad effect on several immune cell types and/or their interactions that are vital for mounting an effective immune response. In this study, we investigated the integrity of plasmacytoid dendritic cell (pDC)-NK cell interactions among HIV viremic, aviremic, and seronegative individuals. We describe a critical defect in the ability of pDCs from HIV-infected individuals to secrete IFN-alpha and TNF and subsequently activate NK cells. We also describe an inherent defect on NK cells from HIV-infected individuals to respond to pDC-secreted cytokines. Furthermore, we were able to demonstrate a direct effect of HIV trimeric gp120 on NK cells in vitro similar to that described ex vivo. Finally, we were able to establish that the HIV gp120-mediated suppressive effect on NK cells was a result of its binding to the integrin alpha(4)beta(7) expressed on NK cells. These findings suggest a novel mechanism by which HIV is capable of suppressing an innate immune function in infected individuals.
- Published
- 2009
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