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Soluble ligands for the NKG2D receptor are released during HIV-1 infection and impair NKG2D expression and cytotoxicity of NK cells.

Abstract

In humans, the interaction of the natural killer group 2 member D (NKG2D)-activating receptor on natural killer (NK) and CD8(+) T cells with its major histocompatibility complex class I-related chain (MIC) and UL16 binding protein (ULBP) ligands (NKG2DLs) promotes recognition and elimination of stressed cells, such as tumor or infected cells. Here, we investigated the capacity of HIV-1 to modulate NKG2DL expression and escape NGK2D-mediated immunosurveillance. In CD4(+) T lymphocytes, both cell surface expression and release of MICA, MICB, and ULBP2 were up-regulated >2-fold by HIV-1 infection. In HIV-infected CD4(+) T lymphocytes or Jurkat T-cell lines, increased shedding of soluble NKG2DLs (sNKG2DLs) was impaired by a matrix metalloproteinase inhibitor (MMPI). Moreover, naive HIV(+) patients displayed increased plasma sMICA and sULBP2 levels and reduced NKG2D expression on NK and CD8(+) T cells compared to patients receiving highly active antiretroviral therapy (HAART) or healthy donors. In individual patients, HAART uptake resulted in the drop of sNKG2DL and recovery of NKG2D expression. Finally, sNKG2DLs in patients' plasma down-regulated NKG2D on NK and CD8(+) T cells and impaired NKG2D-mediated cytotoxicity of NK cells. Thus, NKG2D detuning by sNKG2DLs may promote HIV-1 immune evasion and compromise host resistance to opportunistic infections, but HAART and MMPI have the potential to avoid such immune dysfunction.

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  • Authors+Show Affiliations

    ,

    Laboratory of Immunoinfectivology, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

    , , , , , , , , ,

    Source

    MeSH

    Adolescent
    Adult
    Antiretroviral Therapy, Highly Active
    CD4-Positive T-Lymphocytes
    CD8-Positive T-Lymphocytes
    Case-Control Studies
    Cytotoxicity, Immunologic
    GPI-Linked Proteins
    HIV Infections
    HIV-1
    Histocompatibility Antigens Class I
    Humans
    Intercellular Signaling Peptides and Proteins
    Jurkat Cells
    K562 Cells
    Killer Cells, Natural
    Ligands
    Matrix Metalloproteinase 1
    NK Cell Lectin-Like Receptor Subfamily K
    Young Adult

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    23395909

    Citation

    Matusali, Giulia, et al. "Soluble Ligands for the NKG2D Receptor Are Released During HIV-1 Infection and Impair NKG2D Expression and Cytotoxicity of NK Cells." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 27, no. 6, 2013, pp. 2440-50.
    Matusali G, Tchidjou HK, Pontrelli G, et al. Soluble ligands for the NKG2D receptor are released during HIV-1 infection and impair NKG2D expression and cytotoxicity of NK cells. FASEB J. 2013;27(6):2440-50.
    Matusali, G., Tchidjou, H. K., Pontrelli, G., Bernardi, S., D'Ettorre, G., Vullo, V., ... Doria, M. (2013). Soluble ligands for the NKG2D receptor are released during HIV-1 infection and impair NKG2D expression and cytotoxicity of NK cells. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 27(6), pp. 2440-50. doi:10.1096/fj.12-223057.
    Matusali G, et al. Soluble Ligands for the NKG2D Receptor Are Released During HIV-1 Infection and Impair NKG2D Expression and Cytotoxicity of NK Cells. FASEB J. 2013;27(6):2440-50. PubMed PMID: 23395909.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Soluble ligands for the NKG2D receptor are released during HIV-1 infection and impair NKG2D expression and cytotoxicity of NK cells. AU - Matusali,Giulia, AU - Tchidjou,Hyppolite Kuekou, AU - Pontrelli,Giuseppe, AU - Bernardi,Stefania, AU - D'Ettorre,Gabriella, AU - Vullo,Vincenzo, AU - Buonomini,Anna Rita, AU - Andreoni,Massimo, AU - Santoni,Angela, AU - Cerboni,Cristina, AU - Doria,Margherita, Y1 - 2013/02/08/ PY - 2013/2/12/entrez PY - 2013/2/12/pubmed PY - 2013/8/3/medline KW - MICA/B KW - ULBP KW - immune evasion KW - shedding SP - 2440 EP - 50 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J. VL - 27 IS - 6 N2 - In humans, the interaction of the natural killer group 2 member D (NKG2D)-activating receptor on natural killer (NK) and CD8(+) T cells with its major histocompatibility complex class I-related chain (MIC) and UL16 binding protein (ULBP) ligands (NKG2DLs) promotes recognition and elimination of stressed cells, such as tumor or infected cells. Here, we investigated the capacity of HIV-1 to modulate NKG2DL expression and escape NGK2D-mediated immunosurveillance. In CD4(+) T lymphocytes, both cell surface expression and release of MICA, MICB, and ULBP2 were up-regulated >2-fold by HIV-1 infection. In HIV-infected CD4(+) T lymphocytes or Jurkat T-cell lines, increased shedding of soluble NKG2DLs (sNKG2DLs) was impaired by a matrix metalloproteinase inhibitor (MMPI). Moreover, naive HIV(+) patients displayed increased plasma sMICA and sULBP2 levels and reduced NKG2D expression on NK and CD8(+) T cells compared to patients receiving highly active antiretroviral therapy (HAART) or healthy donors. In individual patients, HAART uptake resulted in the drop of sNKG2DL and recovery of NKG2D expression. Finally, sNKG2DLs in patients' plasma down-regulated NKG2D on NK and CD8(+) T cells and impaired NKG2D-mediated cytotoxicity of NK cells. Thus, NKG2D detuning by sNKG2DLs may promote HIV-1 immune evasion and compromise host resistance to opportunistic infections, but HAART and MMPI have the potential to avoid such immune dysfunction. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/23395909/Soluble_ligands_for_the_NKG2D_receptor_are_released_during_HIV_1_infection_and_impair_NKG2D_expression_and_cytotoxicity_of_NK_cells_ L2 - http://www.fasebj.org/doi/full/10.1096/fj.12-223057?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -