Methamphetamine Administration Targets Multiple Immune Subsets and Induces Phenotypic Alterations Suggestive of Immunosuppression |
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Authors: | Robert Harms Brenda Morsey Craig W Boyer Howard S Fox Nora Sarvetnick |
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Institution: | 1. Department of Surgery-Transplant, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.; 2. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.; 3. Regenerative Medicine Project, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.; Temple University School of Medicine, United States of America, |
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Abstract: | Methamphetamine (Meth) is a widely abused stimulant and its users are at increased risk for multiple infectious diseases. To determine the impact of meth on the immune system, we utilized a murine model that simulates the process of meth consumption in a typical addict. Our phenotypic analysis of leukocytes from this dose escalation model revealed that meth affected key immune subsets. Meth administration led to a decrease in abundance of natural killer (NK) cells and the remaining NK cells possessed a phenotype suggesting reduced responsiveness. Dendritic cells (DCs) and Gr-1high monocytes/macrophages were also decreased in abundance while Gr-1low monocytes/macrophages appear to show signs of perturbation. CD4 and CD8 T cell subsets were affected by methamphetamine, both showing a reduction in antigen-experienced subsets. CD4 T cells also exhibited signs of activation, with increased expression of CD150 on CD226-expressing cells and an expansion of KLRG1+, FoxP3− cells. These results exhibit that meth has the ability to disrupt immune homeostasis and impact key subsets of leukocytes which may leave users more vulnerable to pathogens. |
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