Methamphetamine inhibits antigen processing, presentation, and phagocytosis

Zsolt Tallóczy, Jose Martinez, Danielle Joset, Yonaton Ray, Attila Gácser, Sima Toussi, Noboru Mizushima, Joshua D. Nosanchuk, Harris Goldstein, John Loike, David Sulzer, Laura Santambrogio

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalPLoS Pathogens
Volume4
Issue number2
DOIs
StatePublished - Feb 2008

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Methamphetamine
Antigen Presentation
Phagocytosis
Immunosuppressive Agents
Organelles
Dendritic Cells
Acquired Immunodeficiency Syndrome
Unsafe Sex
Cryptococcus neoformans
Proton-Motive Force
Sexual Partners
Histocompatibility Antigens Class II
Lysosomes
Candida albicans
Coinfection
Macrophages
HIV
Pharmacology
Pathology
T-Lymphocytes

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Methamphetamine inhibits antigen processing, presentation, and phagocytosis. / Tallóczy, Zsolt; Martinez, Jose; Joset, Danielle; Ray, Yonaton; Gácser, Attila; Toussi, Sima; Mizushima, Noboru; Nosanchuk, Joshua D.; Goldstein, Harris; Loike, John; Sulzer, David; Santambrogio, Laura.

In: PLoS Pathogens, Vol. 4, No. 2, 02.2008.

Research output: Contribution to journalArticle

Tallóczy, Z, Martinez, J, Joset, D, Ray, Y, Gácser, A, Toussi, S, Mizushima, N, Nosanchuk, JD, Goldstein, H, Loike, J, Sulzer, D & Santambrogio, L 2008, 'Methamphetamine inhibits antigen processing, presentation, and phagocytosis', PLoS Pathogens, vol. 4, no. 2. https://doi.org/10.1371/journal.ppat.0040028
Tallóczy, Zsolt ; Martinez, Jose ; Joset, Danielle ; Ray, Yonaton ; Gácser, Attila ; Toussi, Sima ; Mizushima, Noboru ; Nosanchuk, Joshua D. ; Goldstein, Harris ; Loike, John ; Sulzer, David ; Santambrogio, Laura. / Methamphetamine inhibits antigen processing, presentation, and phagocytosis. In: PLoS Pathogens. 2008 ; Vol. 4, No. 2.
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