AIDS

Skip Navigation LinksHome > September 10, 2010 - Volume 24 - Issue 14 > Increased plasmacytoid dendritic cell maturation and natural...
AIDS:
doi: 10.1097/QAD.0b013e32833dfc20
Basic Science

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

Tomescu, Costina; Duh, Fuh-Meib; Lanier, Michael Ac; Kapalko, Angelad; Mounzer, Karam Cd; Martin, Maureen Pb; Carrington, Maryb; Metzger, David Sc; Montaner, Luis Ja

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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 KIR3DL1high) 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*80I 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.

© 2010 Lippincott Williams & Wilkins, Inc.

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