Methamphetamine Inhibits Toll-Like Receptor 9-Mediated Anti-HIV Activity in Macrophages

Cen, Ping; Li, Ye; Su, Qi-jian; Xu, Wei; Li, Jieliang; Lin, Xin-Qin; Liang, Hao; Ho, Wen‐Zhe

doi:10.1089/aid.2012.0264

Cited by 21 publications

(15 citation statements)

References 47 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…METH activates lymphocytes and promotes transendothelial migration (Martins et al, 2013 ). METH also increases HIV-1 replication in lymphocytes and increases HIV-1 receptor expression on dendritic cells (Liang et al, 2008 ; Nair et al, 2009 ; Cen et al, 2013 ; Atluri et al, 2015 ). Further, METH exposure suppresses anti-HIV-1 activity in macrophages (MP) by downregulating toll-like receptor-9 expression.…”

Section: Astrocytes In Handmentioning

confidence: 99%

HIV-1, methamphetamine and astrocytes at neuroinflammatory Crossroads

Borgmann

Ghorpade

2015

Front. Microbiol.

View full text Add to dashboard Cite

As a popular psychostimulant, methamphetamine (METH) use leads to long-lasting, strong euphoric effects. While METH abuse is common in the general population, between 10 and 15% of human immunodeficiency virus-1 (HIV-1) patients report having abused METH. METH exacerbates the severity and onset of HIV-1-associated neurocognitive disorders (HAND) through direct and indirect mechanisms. Repetitive METH use impedes adherence to antiretroviral drug regimens, increasing the likelihood of HIV-1 disease progression toward AIDS. METH exposure also directly affects both innate and adaptive immunity, altering lymphocyte numbers and activity, cytokine signaling, phagocytic function and infiltration through the blood brain barrier. Further, METH triggers the dopamine reward pathway and leads to impaired neuronal activity and direct toxicity. Concurrently, METH and HIV-1 alter the neuroimmune balance and induce neuroinflammation, which modulates a wide range of brain functions including neuronal signaling and activity, glial activation, viral infection, oxidative stress, and excitotoxicity. Pathologically, reactive gliosis is a hallmark of both HIV-1- and METH-associated neuroinflammation. Significant commonality exists in the neurotoxic mechanisms for both METH and HAND; however, the pathways dysregulated in astroglia during METH exposure are less clear. Thus, this review highlights alterations in astrocyte intracellular signaling pathways, gene expression and function during METH and HIV-1 comorbidity, with special emphasis on HAND-associated neuroinflammation. Importantly, this review carefully evaluates interventions targeting astrocytes in HAND and METH as potential novel therapeutic approaches. This comprehensive overview indicates, without a doubt, that during HIV-1 infection and METH abuse, a complex dialog between all neural cells is orchestrated through astrocyte regulated neuroinflammation.

show abstract

Section: Astrocytes In Handmentioning

confidence: 99%

HIV-1, methamphetamine and astrocytes at neuroinflammatory Crossroads

Borgmann

Ghorpade

2015

Front. Microbiol.

View full text Add to dashboard Cite

show abstract

“…A review by Purohit et al (2011) nicely illustrates the effects of DA in HIV transcription caused by oxidative stress and NF-κB activation in the presence of drugs of abuse in the brain (reviewed in Purohit et al, 2011 ). Inhibition of phagocytosis, disruption of pH and the reduced expression of Toll-like receptor 9 have each been proposed as mechanisms to explain the MA promotion of spreading HIV infection ( Talloczy et al, 2008 ; Cen et al, 2013 ). In turn, the MA-induced elevation in DA levels seems to induce the migration of activated monocytes into the brain in the context of HIV (reviewed in Gaskill et al, 2013 ; Coley et al, 2015 ).…”

Section: Tat and Methamphetamine Neurotoxicitymentioning

confidence: 99%

The cross-talk of HIV-1 Tat and methamphetamine in HIV-associated neurocognitive disorders

et al. 2015

View full text Add to dashboard Cite

Antiretroviral therapy has dramatically improved the lives of human immunodeficiency virus 1 (HIV-1) infected individuals. Nonetheless, HIV-associated neurocognitive disorders (HAND), which range from undetectable neurocognitive impairments to severe dementia, still affect approximately 50% of the infected population, hampering their quality of life. The persistence of HAND is promoted by several factors, including longer life expectancies, the residual levels of virus in the central nervous system (CNS) and the continued presence of HIV-1 regulatory proteins such as the transactivator of transcription (Tat) in the brain. Tat is a secreted viral protein that crosses the blood–brain barrier into the CNS, where it has the ability to directly act on neurons and non-neuronal cells alike. These actions result in the release of soluble factors involved in inflammation, oxidative stress and excitotoxicity, ultimately resulting in neuronal damage. The percentage of methamphetamine (MA) abusers is high among the HIV-1-positive population compared to the general population. On the other hand, MA abuse is correlated with increased viral replication, enhanced Tat-mediated neurotoxicity and neurocognitive impairments. Although several strategies have been investigated to reduce HAND and MA use, no clinically approved treatment is currently available. Here, we review the latest findings of the effects of Tat and MA in HAND and discuss a few promising potential therapeutic developments.

show abstract

“…METH increases HIV production and viremia in mice transgenic for a replication-competent HIV provirus and human cyclin T1 (Toussi et al, 2009 ). Interestingly, METH's interaction with macrophages has illustrated the down-regulation of TLR9 expression, aiding in the HIV infection of these innate cells by mitigating the receptor's antiviral effects (Cen et al, 2013 ).…”

Section: Meth Facilitates the Acquisition Of Infectious Diseasesmentioning

confidence: 99%

Impact of methamphetamine on infection and immunity

et al. 2015

View full text Add to dashboard Cite

The prevalence of methamphetamine (METH) use is estimated at ~35 million people worldwide, with over 10 million users in the United States. METH use elicits a myriad of social consequences and the behavioral impact of the drug is well understood. However, new information has recently emerged detailing the devastating effects of METH on host immunity, increasing the acquisition of diverse pathogens and exacerbating the severity of disease. These outcomes manifest as modifications in protective physical and chemical defenses, pro-inflammatory responses, and the induction of oxidative stress pathways. Through these processes, significant neurotoxicities arise, and, as such, chronic abusers with these conditions are at a higher risk for heightened consequences. METH use also influences the adaptive immune response, permitting the unrestrained development of opportunistic diseases. In this review, we discuss recent literature addressing the impact of METH on infection and immunity, and identify areas ripe for future investigation.

show abstract

Methamphetamine Inhibits Toll-Like Receptor 9-Mediated Anti-HIV Activity in Macrophages

Cited by 21 publications

References 47 publications

HIV-1, methamphetamine and astrocytes at neuroinflammatory Crossroads

HIV-1, methamphetamine and astrocytes at neuroinflammatory Crossroads

The cross-talk of HIV-1 Tat and methamphetamine in HIV-associated neurocognitive disorders

Impact of methamphetamine on infection and immunity

Contact Info

Product

Resources

About