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Increased plasmacytoid dendritic cell maturation and natural killer cell activation in HIV-1 exposed, uninfected intravenous drug users

  1. Author:
    Tomescu, C.
    Duh, F. M.
    Lanier, M. A.
    Kapalko, A.
    Mounzer, K. C.
    Martin, M. P.
    Carrington, M.
    Metzger, D. S.
    Montaner, L. J.

  2. Author Address

    [Tomescu, Costin; Montaner, Luis J.] Wistar Inst Anat & Biol, HIV Immunopathogenesis Lab, Philadelphia, PA 19104 USA. [Duh, Fuh-Mei; Martin, Maureen P.; Carrington, Mary] NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. [Duh, Fuh-Mei; Martin, Maureen P.; Carrington, Mary] MGH MIT & Harvard, Ragon Inst, Boston, MA USA. [Lanier, Michael A.; Metzger, David S.] Univ Penn, Dept Psychiat, HIV Prevent Div, Philadelphia, PA 19104 USA. [Kapalko, Angela; Mounzer, Karam C.] Jonathan Lax Treatment Ctr, Philadelphia FIGHT, Philadelphia, PA USA.;Montaner, LJ, Wistar Inst Anat & Biol, HIV Immunopathogenesis Lab, 3601 Spruce St,Room 480, Philadelphia, PA 19104 USA.;Montaner@wistar.org
    1. Year: 2010
    2. Date: Sep
  2. Journal: Aids
    1. 24
    2. 14
    3. Pages: 2151-2160
  4. Type of Article: Article
  5. ISSN: 0269-9370
  1. Abstract:

    Background: Increased natural killer (NK) activation has been associated with resistance to HIV-1 infection in several cohorts of HIV-1 exposed, uninfected individuals. Inheritance of protective NK receptor alleles (KIR3DS1 and KIR3DL1(high)) has also been observed in a subset of HIV-1 exposed, uninfected individuals. However, the exact mechanism contributing to NK activation in HIV-1 exposed, uninfected intravenous drug users (EU-IDU) remains to be elucidated. Objective: We investigated the role of both host genotype and pathogen-induced dendritic cell modulation of NK activation during high-risk activity in a cohort of 15 EU-IDU individuals and 15 control, uninfected donors from Philadelphia. Design: We assessed the activation status of NK cells and dendritic cells by flow cytometry and utilized functional assays of NK-DC cross-talk to characterize the innate immune compartment in EU-IDU individuals. Results: As previously reported, NK cell activation (CD69) and/or degranulation (CD107a) was significantly increased in EU-IDU individuals compared with control uninfected donors (P = 0.0056, n = 13). Genotypic analysis indicated that the frequency of protective KIR (KIR3DS1) and HLA-Bw4*801 ligands was not enriched in our cohort of EU-IDU individuals. Rather, plasmacytoid dendritic cells (PDC) from EU-IDU exhibited heightened maturation (CD83) compared with control uninfected donors (P = 0.0011, n = 12). When stimulated in vitro, both PDCs and NK cells from EU-IDU individuals maintained strong effector cell function and did not exhibit signs of exhaustion. Conclusion: Increased maturation of PDCs is associated with heightened NK activation in EU-IDU individuals suggesting that both members of the innate compartment may contribute to resistance from HIV-1 infection in EU-IDU. (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

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External Sources

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  2. DOI: 10.1097/QAD.0b013e32833dfc20
  3. View record in Web of Science®
  4. WOS: 000281249200002

Library Notes

  1. Fiscal Year: FY2009-2010
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