1. Defective plasmacytoid dendritic cell-NK cell cross-talk in HIV infection.
- Author
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Reitano KN, Kottilil S, Gille CM, Zhang X, Yan M, O'Shea MA, Roby G, Hallahan CW, Yang J, Lempicki RA, Arthos J, and Fauci AS
- Subjects
- HIV Envelope Protein gp120 immunology, HIV Envelope Protein gp120 metabolism, Humans, Integrins metabolism, Interferon-alpha metabolism, Protein Binding, Tumor Necrosis Factor-alpha metabolism, Viremia immunology, Dendritic Cells immunology, HIV Infections immunology, Killer Cells, Natural immunology
- 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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