ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Morphine modulation of toll-like receptors in microglial cells potentiates neuropathogenesis in a HIV-1 model of coinfection with pneumococcal pneumoniae.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 48 citations in OpenAlex.
- Pharmacokinetic and neuroimmune pharmacogenetic impacts on slow-release morphine cancer pain control and adverse effects.The pharmacogenomics journal · 2024Article
- The Interplay between Chronic Pain, Opioids, and the Immune System.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2022Review
- Chronic Low Dose Morphine Does Not Alter Two In Vitro BBB Models.Brain sciences · 2022Article
- Morphine-induced microglial immunosuppression via activation of insufficient mitophagy regulated by NLRX1.Journal of neuroinflammation · 2022Article
- Improving translational relevance: The need for combined exposure models for studying prenatal adversity.Brain, behavior, & immunity - health · 2021Article
- Review
- Opioid-Mediated HIV-1 Immunopathogenesis.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- Opioid and neuroHIV Comorbidity - Current and Future Perspectives.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- Morphine-mediated release of miR-138 in astrocyte-derived extracellular vesicles promotes microglial activation.Journal of extracellular vesicles · 2020Article
- Neuroinflammation & pre-mature aging in the context of chronic HIV infection and drug abuse: Role of dysregulated autophagy.Brain research · 2019Review
- The impact of substance abuse on HIV-mediated neuropathogenesis in the current ART era.Brain research · 2019Review
- The Role of Opioid Receptors in Immune System Function.Frontiers in immunology · 2019Review
- Microglia Express Mu Opioid Receptor: Insights From Transcriptomics and Fluorescent Reporter Mice.Frontiers in psychiatry · 2018Article
- In vitro modeling of HIV proviral activity in microglia.The FEBS journal · 2017Article
- Soluble TLR2 and 4 concentrations in cerebrospinal fluid in HIV/SIV-related neuropathological conditions.Journal of neurovirology · 2017Article
- Toll-like receptor 3 activation selectively reverses HIV latency in microglial cells.Retrovirology · 2017Article
- Gut Homeostasis, Microbial Dysbiosis, and Opioids.Toxicologic pathology · 2017Review
- Opioid-induced gut microbial disruption and bile dysregulation leads to gut barrier compromise and sustained systemic inflammation.Mucosal immunology · 2016Article
- Neuroprotective role of galectin-1 in central nervous system pathophysiology.Neural regeneration research · 2016Article
- Cocaine-mediated induction of microglial activation involves the ER stress-TLR2 axis.Journal of neuroinflammation · 2016Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Chronic drug users account for a third of all cases of AIDS in the United States and the progression to AIDS dementia is accelerated in opiate drug abusers. Clinically, microglial activation better correlates with HIV-associated neurocognitive disorders (HAND) than productive HIV-1 infection in the CNS. Moreover, pneumococcal pneumonia is the most common opportunistic infection in individuals with HAND. We show that coinfection with Streptococcus pneumoniae may be a contributing factor in the increased prevalence of HAND in the opioid-dependent population. To date, there have been no studies published implicating the Toll-like receptors (TLR) in the neurocognitive disorders associated with NeuroAIDS in the context of opportunistic infection. Our studies show for the first time, in a morphine-dependent model, synergistic increase and activation of TLR expression in the presence of HIV-1 protein TAT and S. pneumoniae with a significant increase in proinflammatory cytokines (IL-6, TNF-α) levels. Furthermore, concurrent increases in reactive oxygen species and nitric oxide production leading to increased caspase 3 activation are also observed in both murine and human microglial cells. These effects are recapitulated with TLR 2, 4, and 9 cognate ligands (Pam3CSK4, LPS, and CpG) and significantly attenuated in TLR 2 and 4 knock-out mice and TLR2/4 double knock-out mice. Therefor, our findings clearly suggest for the first time that activation of TLRs on microglia cells by morphine and TAT in the context of S. pneumoniae infection may be a potential mechanism for the increased prevalence of HAND in HIV-infected opioid-dependent patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.