Methamphetamine Inhibits Antigen Processing, Presentation, and Phagocytosis

PLoS Pathogens

Noboru Mizushima¹  Attila Gácser²  Josh Nosanchuk²  Harris Goldstein³  John Loike³  Sima Toussi³  Zsolt Tallóczy⁴  Laura Santambrogio⁴  Jose Martinez⁵  Danielle Joset⁶  Yonaton Ray⁶  David Sulzer⁶ 

[1] Department of Bioregulation and Metabolism, The Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo, Japan;Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America;Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America;Department of Neurology, Columbia University, New York, New York, United States of America;Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, United States of America;Department of Physiology, Columbia University, New York, New York, United States of America

关键词: Macrophages;    Dendritic cells;    Lysosomes;    Phagocytosis;    Cellular structures;    organelles;    T cells;    Endosomes;    HIV;   

DOI  :  10.1371/journal.ppat.0040028

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY