Increased plasmacytoid dendritic cell maturation and natural killer cell activation in HIV-1 exposed, uninfected intravenous drug users
| Autor: | Costin Tomescu, Maureen P. Martin, Angela Kapalko, Mary Carrington, Fuh-Mei Duh, David S. Metzger, Karam Mounzer, Michael A Lanier, Luis J. Montaner |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Immunology Enzyme-Linked Immunosorbent Assay HIV Infections Plasmacytoid dendritic cell Biology Lymphocyte Activation Article Natural killer cell Immune system Interferon HIV Seronegativity medicine Humans Immunology and Allergy Substance Abuse Intravenous Philadelphia Innate immune system Degranulation virus diseases Dendritic Cells Dendritic cell Flow Cytometry Killer Cells Natural Infectious Diseases medicine.anatomical_structure HIV-1 Female Natural killer cell activation medicine.drug |
| Zdroj: | AIDS. 24:2151-2160 |
| ISSN: | 0269-9370 |
| DOI: | 10.1097/qad.0b013e32833dfc20 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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