Methamphetamine Inhibits Antigen Processing, Presentation, and Phagocytosis

October 12, 2012

Methamphetamine (Meth) is abused by over 35 million people worldwide. Chronic Meth abuse may be particularly devastating in individuals who engage in unprotected sex with multiple partners because it is associated with a 2-fold higher risk for obtaining HIV and associated secondary infections. We report the first specific evidence that Meth at pharmacological concentrations exerts a direct immunosuppressive effect on dendritic cells and macrophages. As a weak base, Meth collapses the pH gradient across acidic organelles, including lysosomes and associated autophagic organelles. This in turn inhibits receptor-mediated phagocytosis of antibody-coated particles, MHC class II antigen processing by the endosomal–lysosomal pathway, and antigen presentation to splenic T cells by dendritic cells. More importantly Meth facilitates intracellular replication and inhibits intracellular killing of Candida albicans and Cryptococcus neoformans, two major AIDS-related pathogens. Meth exerts previously unreported direct immunosuppressive effects that contribute to increased risk of infection and exacerbate AIDS pathology.

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  • Ethan Perlstein

    Methamphetamine act as an immunosuppressant by alkalinizing vesicular cargo trafficking pathways of antigen-presenting cells, e.g., dendritic cells. In other words, the immunosuppressive effects have nothing to do with dopamine release per se. Instead, they arise because meth is a weak base and its accumulation disrupts natural chemical equilibria such as ion gradients.

    So what do you think meth accumulation does to synapses, whose function depends on many natural chemical equilibria?