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Defective Plasmacytoid Dendritic Cell-NK Cell Cross-Talk in HIV Infection

  1. Author:
    Reitano, K. N.
    Kottilil, S.
    Gille, C. M.
    Zhang, X.
    Yan, M.
    O'Shea, M. A.
    Roby, G.
    Hallahan, C. W.
    Yang, J.
    Lempicki, R. A.
    Arthos, J.
    Fauci, A. S.

  2. Author Address

    Reitano, K. N.; Kottilil, S.; Gille, C. M.; Zhang, X.; Yan, M.; Yang, J.; Lempicki, R. A.; Arthos, J.; Fauci, A. S.] NIAID, Immunoregulat Lab, NIH, Dept Hlth & Human Serv, Frederick, MD 21702 USA. [O'Shea, M. A.; Roby, G.] NIH, Dept Crit Care Med, Ctr Clin, Dept Hlth & Human Serv, Frederick, MD 21702 USA. [Hallahan, C. W.] NCI, Biostat Res Branch, NIAID, NIH,Dept Hlth & Human Serv,SAIC Frederick, Frederick, MD 21702 USA.
    1. Year: 2009
  2. Journal: Aids Research and Human Retroviruses
    1. 25
    2. 10
    3. Pages: 1029-1037
  4. Type of Article: Article
  1. 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.

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  2. DOI: 10.1089/aid.2008.0311
  3. PMID: 19795986

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