There is currently a serious opioid abuse epidemic, and opioid drug overdose deaths have more than tripled since 1999. Much of this crisis has been fueled by the synthetic opioid fentanyl that is used clinically for pain management, and is now widely available. Currently, the combination of heroin with fentanyl has grown more common, and may be responsible for up to half of the opioid overdose deaths.

Opiates induce substantial changes in the status of the immune system, and it is apparent that intravenous opioid drug abusers are more susceptible to a variety of both bacterial and viral infectious agents. Intravenous drug use is a primary route of HIV infection in a number of countries (10% of cases worldwide), and the effect of opiate use on HIV pathogenesis is particularly apparent in several organ systems, including the CNS and the lung. There is evidence that opiate abuse can accelerate the progression of HIV infection towards AIDS, and this is likely due to a combination of opioid-induced changes in the status of the immune system. For example, opioid abuse is itself leading to an inflammatory reaction in both the brain and lungs, due to the activation of mu opioid receptors (MOR). When opioid use occurs in the HIV-infected individual, neuroinflammation becomes more exaggerated, and the inflammation in the lungs leads to emphysema.

These issues point out the broad spectrum of influences that opioids have on cells of the immune system, including:
• Increased expression of some pro-inflammatory cytokines and chemokines (e.g., CCL2, CCL5, CXCL10, TGFβ)
• Activation of several pro-inflammatory transcription factors (e.g., NF-κB, STAT1)
• Inhibition of pro-inflammatory cytokines expression (e.g., TNF-α)
• Inhibition of natural killer cell activity
• Inhibition of antibody responses in certain situations
• Induction of some pro-inflammatory chemokine receptors (e.g., CCR5 and CXCR4)
• Induction of apoptosis of susceptible cell populations
• Modulation of inflammatory pain sensitivity
• Cross-talk between opioid and chemokine receptors

This Research Topic will provide a comprehensive overview on the role of opioid receptors in immune functions. We welcome the submission of Reviews, Mini-Reviews and Original Research articles strictly related to the immunological implications in the following subjects:
• CXCR4-MOR cross-talk and neuronal function in HIV infection
• Opioids and oxidative stress and HIV
• Opioid influences on HIV and hepatitis C virus co-infections
• Mechanisms for opioid and HIV induced neuropathology
• Peripheral opioid receptor expression and inflammatory pain responses
• Opioids and monocyte trafficking across the blood-brain barrier
• Immunomodulatory actions of opioids on T cells
• Neuroinflammatory actions of opioids in non-human primates
• Opioid receptor function in the regulation of chronic inflammatory pain
• Opioid-induced miRNAs which regulate apoptosis
• Mechanisms controlling opioid influences on pain
• Sex differences and opioid effects on the immune system
• Opioid receptors and CNS pain circuits
• Opioids and microbial translocation in the gut: influences on the immune system
• Heterologous desensitization between opioid and chemokine receptors: relevance to HIV
• Opioid modulation of the gut microbiome and its impact on gut immune brain axis

We believe this collection is very timely, given the current opioid crisis. A great deal of progress is currently being made to understand both the molecular and biochemical mechanisms which are responsible for the broad spectrum of opioid influences on the immune response.

Keywords: opioid, neuroinflammation, HIV, pain, chemokine

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.