Skip to main content

Advertisement

Log in

Immunology as it Pertains to Drugs of Abuse, AIDS and the Neuroimmune Axis: Mediators and Traffic

  • INVITED REVIEW
  • Published:
Journal of Neuroimmune Pharmacology Aims and scope Submit manuscript

Abstract

The interactions between the immune and nervous systems are very complex, and yet our understanding of these interactions is still relatively limited. The neuroinflammatory reaction that can accompany HIV infection occurs because of a cascade of events that appears to require the migration of HIV-infected cells across the blood–brain barrier. In susceptible individuals, this leads to inflammatory processes which can include substantial changes in neuronal function. It is possible to consider the inflammatory events to be composed of two essential processes. The first process is cellular traffic, and the second, is the expression and recognition of the various pro-inflammatory and/or toxic mediators. The added complication of drug abuse adds complexity to the traffic and mediator release events, and depending on the specific drug being abused, the disease can be exacerbated in these individuals. An understanding of the fine details of these mediator and traffic processes should provide useful targets for therapeutic intervention to attenuate disease associated with HIV infection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

General Readings: The following references provide sections with a general discussion of the area of neuroimmune pharmacology. These texts are well referenced and can be used as a starting point for more extensive research.

  • Gendelman HE, Grant I, Everall IP, Lipton SA, and Swindells S (eds) (2005) The neurology of AIDS, 2nd ed. Oxford University Press, ISBN: 0-19-852610-5

  • Ikezu T, Gendelman HE (eds) (2008) An overview: neuroimmune pharmacology. Springer Science, New York

    Google Scholar 

Reviews of Specific Areas: A. Innate immunity and inflammation. The following references provide a discussion of cells of the innate immune system, the soluble mediators which are important for the inflammatory response, and the receptors that are critical for the evolution of the inflammatory response.

The following review describes the basic biology of the cell considered the first line of defense against microbial infectious agents. It includes a discussion of mechanisms of phagocytosis and the biochemistry of microbicidal activity.

  • Soehnlein O, Lindbom L (2010) Phagocyte partnership during the onset and resolution of inflammation. Nat Rev Immunol 10:427–439

    Article  CAS  PubMed  Google Scholar 

The following is an excellent review of the cellular interactions involved in the traffic of phagocytic cells to sites of inflammation, and the mediators which control these interactions. An outstanding discussion of the phases of inflammatory response.

  • Barton GM, Kagan JC (2009) A cell biological view of toll-like receptor function: regulation through compartmentalization. Nat Rev Immunol 9:535–542

    Article  CAS  PubMed  Google Scholar 

  • Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519–550

    Article  CAS  PubMed  Google Scholar 

  • Luo B-H, Carman CV, Springer TA (2007) Structural basis of integrin regulation and signaling. Annu Rev Immunol 25:619–647

    Article  CAS  PubMed  Google Scholar 

  • Sims JE, Smith DE (2010) The IL-1 family: regulators of immunity. Nat Rev Immunol 10:89–102

    Article  CAS  PubMed  Google Scholar 

  • Watts TH (2005) TNF/TNFR family members in costimulation of T cell responses. Annu Rev Immunol 23:23–68

    Article  CAS  PubMed  Google Scholar 

B. Adaptive Immunity. The papersin this section review many of the cell populations that are responsible for acquired immunity, the receptors expressed by these cells, and the soluble mediators produced by these diverse leukocytes. CD4-expressing T cells provide “help” to both B cells and CD8+ T cells. The following review describes the complexities that are a part of the interactions between these two T cell populations.

  • Castellino F, Germain RN (2006) Cooperation between CD4+ and CD8+ T cells: when, where, and how. Annu Rev Immunol 24:519–540

    Article  CAS  PubMed  Google Scholar 

An excellent overview of the T H 1, T H 2, and T H 17 cell populations, and the molecular basis for the expression of cytokines in these individual sub-populations. The following review also describes a population of “inducible” regulatory T cells (“iTreg”) that contribute to the down-regulation of effector T cell activity.

  • Zhu J, Yamane H, Paul WE (2010) Differentiation of effector CD4 T cell populations. Annu Rev Immunol 28:445–489

    Article  CAS  PubMed  Google Scholar 

The following is an excellent review of the functional activity of “natural” (or “non-inducible”) regulatory T cells and the contribution of these cells during the immune response to certain infectious agents.

  • Belkaid Y, Tarbell K (2009) Regulatory T cells in the control of host–microorganism interactions. Annu Rev Immunol 27:551–589

    Article  CAS  PubMed  Google Scholar 

  • Randolph GJ, Ochando J, Partida-Sanchez S (2008) Migration of dendritic cell subsets and their precursors. Annu Rev Immunol 26:293–316

    Article  CAS  PubMed  Google Scholar 

  • Sakaguchi S, Miyara M, Costantino CM, Hafler DA (2010) FoxP3+ regulatory T cells in the human immune system. Nat Rev Immunol 10:490–500

    Article  CAS  PubMed  Google Scholar 

  • Woodland DL, Kohlmeier JE (2009) Migration, maintenance and recall of memory T cells in peripheral tissues. Nat Rev Immunol 9:153–161

    Article  CAS  PubMed  Google Scholar 

References Randolph et al (2008) and Woodland and Kohlmeier (2009) describe the trafficking of dendritic and T cell populations that occurs as a part of the adapative immune response. These excellent reviews point out the critical role of cell mobility for the immune response.

  • Auffray C, Sieweke MH, Geissmann F (2009) Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol 27:669–692

    Article  CAS  PubMed  Google Scholar 

  • Geissmann F, Gordon S, Hume DA, Mowatt AM, Randolph GJ (2010) Unravelling mononuclear phagocyte heterogeneity. Nat Rev Immunol 10:453–460

    Article  CAS  PubMed  Google Scholar 

  • Martinez FO, Helming L, Gordon S (2009) Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol 27:451–483

    Article  CAS  PubMed  Google Scholar 

  • Pollard JW (2009) Trophic macrophages in development and disease. Nat Rev Immunol 9:259–270

    Article  CAS  PubMed  Google Scholar 

References Auffray et al (2009), Martinez et al. (2009), Pollard (2009) and Geissmann et al. (2010) describe monocyte and macrophage biology and the role of these cells in the immune response. These papers also discuss the heterogeneity in the functional activity of these cells, and the importance of this diversity in certain inflammatory disease states.

  • Ma A, Koka R, Burkett P (2006) Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. Annu Rev Immunol 24:657–679

    Article  CAS  PubMed  Google Scholar 

  • Theofilopoulos AN, Baccala R, Beutler B, Kono DH (2005) Type I interferons (α/β) in immunity and autoimmunity. Annu Rev Immunol 23:307–336

    Article  CAS  PubMed  Google Scholar 

C. Chemoattractants. These reviews describe some of the endogenous chemoattractants that are involved in both innate and adapative immune responses. It should be appreciated that the chemoattractants described in these papers represent only a small fraction of the total number of chemoattractants that are produced in a given tissue, particularly during an inflammatory response.

  • Allen SJ, Crown SE, Handel TM (2007) Chemokine:Receptor structure, interactions, and antagonism. Annu Rev Immunol 25:787–820

    Article  CAS  PubMed  Google Scholar 

  • Cyster JG (2005) Chemokines, Sphingosine-1-phosphate, and cell migration in secondary lymphoid organs. Annu Rev Immunol 23:127–159

    Article  CAS  PubMed  Google Scholar 

  • Zhang N, Oppenheim JJ (2005) Crosstalk between chemokines and neuronal receptors bridges immune and nervous systems. J Leukoc Biol 78:1210–1214

    Article  CAS  PubMed  Google Scholar 

D. Blood–Brain Barrier and Leukocyte Traffic into the Brain. A critical element of neuroinflammatory reactions is the migration of cells of the immune response across the blood-brain barrier. This process involves the active participation of several cell populations, and requires several biochemical events on the vascular endothelial surface in order for leukocyte migration to occur.

  • Banks WA, Erickson MA (2010) The blood–brain barrier and immune function and dysfunction. Neurobiol Dis 37:26–32

    Article  CAS  PubMed  Google Scholar 

  • Persidsky Y, Poluektova L (2006) Immune privilege and HIV-1 persistence in the CNS. Immunol Rev 213:180–94

    Article  CAS  PubMed  Google Scholar 

  • Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD (2006) Blood–brain barrier: structural components and function under physiologic and pathologic conditions. J Neuroimmune Pharmacol 1(3):223–36

    Article  PubMed  Google Scholar 

  • Roberts TK, Buckner CM, Berman JW (2010) Leukocyte transmigration across the blood–brain barrier: perspectives on neuroAIDS. Front Biosci 15:478–536

    Article  CAS  PubMed  Google Scholar 

E. Drugs of Abuse and the Immune Response. Most of the drugs of abuse exert effects on the immune system, and the literature suggests that both innate and adaptive immunity is modulated by these drugs. Several excellent reviews have recently been published which describe the activities of opioids, cannabinoids, cocaine and alcohol on cells of the immune system.

  • Achur RN, Freeman WM, Vrana KE (2010) Circulating cytokines as biomarkers of alcohol abuse and alcoholism. J Neuroimmune Pharmacol 5:83–91

    Article  PubMed  Google Scholar 

  • Bidlack JM, Khimich M, Parkhill AL, Sumagin S, Sun B, Tipton CM (2006) Opioid receptors and signaling on cells from the immune system. J Neuroimmune Pharmacol 1:260–269

    Article  PubMed  Google Scholar 

  • Cabral GA, Griffin-Thomas L (2009) Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation. Expert Rev Mol Med 11:e3

    Article  PubMed  Google Scholar 

  • Eisenstein TK, Rahim RT, Feng P, Thingalaya NK, Meissler JJ (2006) Effects of opioid tolerance and withdrawal on the immune system. J Neuroimmune Pharmacol 1:237–249

    Article  PubMed  Google Scholar 

  • Ferris MJ, Mactutus CF, Booze RM (2008) Neurotoxic profiles of HIV, psychostimulant drugs of abuse, and their concerted effect on the brain: current status of dopamine system vulnerability in NeuroAIDS. Neurosci Biobehav Rev 32:883–909

    Article  CAS  PubMed  Google Scholar 

  • Finley MJ, Happel CM, Kaminsky DE, Rogers TJ (2008) Opioid and nociceptin receptors regulate cytokine and cytokine receptor expression. Cell Immunol 252:146–54

    Article  CAS  PubMed  Google Scholar 

  • Klein TW, Cabral GA (2006) Cannabinoid-induced immune suppression and modulation of antigen-presenting cells. J Neuroimmune Pharmacol 1:50–64

    Article  PubMed  Google Scholar 

  • Machelska H, Stein C (2006) Leukocyte-derived opioid peptides and inhibition of pain. J Neuroimmune Pharmacol 1:90–97

    Article  PubMed  Google Scholar 

  • Molina PE (2006) Opioids and opiates: analgesia with cardiovascular, haemodynamic and immune implications in critical illness. J Int Med 259:138–154

    Article  CAS  Google Scholar 

  • Szabo G, Mandrekar P (2009) A recent perspective on alcohol, immunity, and host defense. Alcohol Clin Exp Res 33:220–232

    Article  CAS  PubMed  Google Scholar 

  • Ugen KE, Nyland SB (2006) Injecting drugs of abuse and immunity: implications for HIV vaccine testing and efficacy. Springer Semin Immunopathol 28:281–7

    Article  PubMed  Google Scholar 

E. Neurodegeneration and AIDS. These reviews describe innate immune responses in the brain, and the inflammatory processes that occur in the brain that are responsible for the neurodegeneration that can be associated with HIV infection. These papers provide an overview of inflammation in the brain, and the cells and mediators that are particularly critical for inflammation at this specific tissue site.

  • Gonzalez-Scarano F, Martin-Garcia J (2005) The neuropathogenesis of AIDS. Nat Rev Immunol 5:69–81

    Article  CAS  PubMed  Google Scholar 

  • Hauser KF, El-Hage N, Stiene-Martin A, Maragos WF, Nath A, Persidsky Y, Volsky DJ, Knapp PE (2007) HIV-1 neuropathogenesis: glial mechanisms revealed through substance abuse. J Neurochem 100:567–578

    Article  CAS  PubMed  Google Scholar 

  • Kraft-Terry SD, Stothert AR, Buch S, Gendelman HE (2010) HIV-1 neuroimmunity in the era of antiretroviral therapy. Neurobiol Dis 37:542–548

    Article  CAS  PubMed  Google Scholar 

  • McMichael AJ, Borrow P, Tomaras GD, Goonetilleke N, Haynes BF (2010) The immune response during acute HIV-1 infection: clues for vaccine development. Nat Rev Immunol 10:11–23

    Article  CAS  PubMed  Google Scholar 

  • Rivest S (2009) Regulation of innate immune responses in the brain. Nat Rev Immunol 9:429–439

    Article  CAS  PubMed  Google Scholar 

Download references

Source of Support

Supported, in part, by NIH grants DA-14230, DA-25532, PO1DA-23860, and P30DA-13429.

Conflict of Interest Disclosure

The author has neither a financial nor a personal relationship which might bias this work.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thomas J. Rogers.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rogers, T.J. Immunology as it Pertains to Drugs of Abuse, AIDS and the Neuroimmune Axis: Mediators and Traffic. J Neuroimmune Pharmacol 6, 20–27 (2011). https://doi.org/10.1007/s11481-010-9247-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11481-010-9247-2

Keywords

Navigation