Persons who inject drugs (PWID) retain functional NK cells, dendritic cell stimulation, and adaptive immune recall responses despite prolonged opioid use
Year: 2020
Type: article
Study design: Observational Study
Abstract: Previous literature suggests that acute opioid use results in the functional impairment of the immune response, thereby decreasing resistance to viral infection. Here, we assessed if innate and adaptive immune responses are compromised ex vivo in persons who inject drugs (PWID) and whether long-term injection drug use may impact host susceptibility to in vitro HIV infection. We measured the frequency, activation state, and functional profile of NK cells, dendritic cells, and CD4+ and CD8+ T cells in low-risk PWID who do not share needles, high-risk needle-sharing PWID, and control donors who did not inject drugs. We also assessed plasma levels of inflammatory markers and CD4+ T cell susceptibility to HIV infection. We observed a significant increase in the amount of sCD14 (P = 0.0023, n = 16) and sCD163 (P = 0.0001, n = 16) in the plasma of PWID compared to controls. Evidence of constitutive activation was noted in PWID as compared to controls with increased CD69 expression in CD56dim NK cells (P = 0.0103, n = 26) and increased CD38 and HLA-DR expression in CD4+ T cells (P = 0.0355, n = 23). However, no innate or adaptive functional differences were detected between PWID and controls, including: NK cell direct or antibody-dependent cellular cytotoxicity poly-functional response, TLR-stimulated dendritic cell/NK crosstalk, CD8+ T cell response to Staphylococcal enterotoxin B or CMV/EBV/FLU peptides, or constitutive or anti-CD3/CD28-stimulated CD4+ T cell infectivity with CCR5-tropic or CXCR4-tropic HIV-1 isolates. Our data indicate that PWID who utilize opioids over as prolonged time frame can retain a functional ex vivo immune response without a measurable increase in CD4+ T cell infectivity suggesting that leukocytes from PWID are not intrinsically more susceptibility to infection with HIV than non-PWID controls.
Source: Journal of Leukocyte Biology
Authors: Costin Tomescu, Krystal Colon, Peter Smith, Mack Taylor, Livio Azzoni, David S Metzger, Luis J Montaner
Institutions: The Wistar Institute, University of Pennsylvania
Language: English
Topic: HIV, Drug Use, Sexual Risk
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: National Science Foundation, Pennsylvania Department of Health, University of Arizona Cancer Center, Philadelphia Foundation, National Institutes of Health, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute of Allergy and Infectious Diseases
Awards: G1047360950, G1214792496, G1239849830, G1524506673, G2197626812, Mechanisms of Resistance in HIV-1 Exposed Sero-negative IV-drug Users: Induction of IFN-mediated Factors and S100 Proteins as Determinants of NK Cell-Mediated Clearance and Low CD4+ T Cell Infectivity, BEAT-HIV: Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy, G3362366791, HIV Pathogenesis, Vaccination and Cure, Early Innate/IgA Anti-HIV/SIV Response in Exposed Uninfected, G547379174, G569728671, G637192391, G6728089788, G6959981662, G7011788827, G707050422, G7489913356, NK Cell Activation and Function in HIV-1 Exposed Uninfected IV Drug Users, Effects of Mu-opiate receptor engagement on the persistence of HIV-associated activation and viral reservoirs in individuals receiving medication assisted treatment for opioid use disorder, G7957613251, Effects of mu-opiate receptor engagement on microbial translocation and residual immune activation in HIV-infected, ART suppressed opioid use disorder patents initiating medication-assisted treatment, G8127585434, G9000031053, G9000097743, G9000235472, G9000242278, G9000245565, Penn Mental Health AIDS Research Center, Consolidated Basic Cancer Research Program
OpenAlex ID: W3107523215