Methamphetamine Enhances Histoplasmosis by Immunosuppression of the Host

• DOI: 10.1086/599328
• Publication Date: 2009-05-27T21:42:55Z
• Authors: Luis R. Martinez; Mircea Radu Mihu; Attila Gácser; Laura Santambrogio; Joshua D. Nosanchuk
• Keywords: Immunosuppression; Methamphetamine; Histoplasma

The effect of methamphetamine on the host response to an opportunistic pathogen has not been extensively described. Methamphetamine is a major public health and safety problem in United States. Chronic abuse associated with 2-fold higher risk human immunodeficiency virus infection and, possibly, additional infections. Histoplasma capsulatum dimorphic fungus that endemic Midwest States causes respiratory systemic disease, particularly individuals impaired immunity. We showed abrogates normal macrophage function, resulting inability control histoplasmosis. decreased phagocytosis killing yeast by primary macrophages alkalization phagosome. Furthermore, mice received prior H. were immunologically impaired, increased fungal burden, pulmonary inflammation, survival. Immunosuppression may be deregulation cytokines lungs infected mice, aberrant processing within macrophages, immobilization MAC-1 receptors surface are involved phagocytosis. Additionally, inhibits T cell proliferation alters antibody production, which important components adaptive With use murine model histoplasmosis, this study establishes alter immune system enhance pathogenesis.