Alcohol enhances type 1 interferon-α production and mortality in young mice infected with Mycobacterium tuberculosis
| Autor: | Steve Nelson, Padmaja Paidipally, Kamakshi Prudhula Devalraju, Ramakrishna Vankayalapati, Deepak Tripathi, Elwyn Welch, Venkata Sanjeev Kumar Neela, Rajesh Kumar Radhakrishnan, Vijaya Lakshmi Valluri, Sambasivan Venkatasubramanian, Abhinav Van, Carol M. Mason, Satyanarayana Swamy Cheekatla, Buka Samten |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Confocal Microscopy Social Sciences Mice White Blood Cells Animal Cells Medicine and Health Sciences Psychology Medicine Macrophage lcsh:QH301-705.5 Microscopy Alcohol Consumption biology Latent tuberculosis Organic Compounds Light Microscopy respiratory system Addicts 3. Good health Actinobacteria Chemistry Integrin alpha M Physical Sciences Female Disease Susceptibility Cellular Types Antibody Research Article Adult lcsh:Immunologic diseases. Allergy Alcohol Drinking Death Rates Immune Cells Necroptosis Immunology Addiction Research and Analysis Methods Microbiology Peripheral blood mononuclear cell Mycobacterium tuberculosis 03 medical and health sciences Immune system Population Metrics Latent Tuberculosis Virology Genetics Animals Humans Tuberculosis Alcoholics Molecular Biology Nutrition Blood Cells Bacteria Population Biology business.industry Macrophages Organic Chemistry Organisms Chemical Compounds Interferon-alpha Biology and Life Sciences Cell Biology bacterial infections and mycoses biology.organism_classification medicine.disease Diet 030104 developmental biology lcsh:Biology (General) Alcohols biology.protein Parasitology lcsh:RC581-607 business |
| Zdroj: | PLoS Pathogens, Vol 14, Iss 8, p e1007174 (2018) PLoS Pathogens |
| ISSN: | 1553-7374 |
| DOI: | 10.1371/journal.ppat.1007174 |
| Popis: | In the current study, we used a mouse model and human blood samples to determine the effects of chronic alcohol consumption on immune responses during Mycobacterium tuberculosis (Mtb) infection. Alcohol increased the mortality of young mice but not old mice with Mtb infection. CD11b+Ly6G+ cells are the major source of IFN-α in the lungs of Mtb-infected alcohol-fed young mice, and IFN-α enhances macrophage necroptosis in the lungs. Treatment with an anti-IFNAR-1 antibody enhanced the survival of Mtb-infected alcohol-fed young mice. In response to Mtb, peripheral blood mononuclear cells (PBMCs) from alcoholic young healthy individuals with latent tuberculosis infection (LTBI) produced significantly higher amounts of IFN-α than those from non-alcoholic young healthy LTBI+ individuals and alcoholic and non-alcoholic old healthy LTBI+ individuals. Our study demonstrates that alcohol enhances IFN-α production by CD11b+Ly6G+ cells in the lungs of young Mtb-infected mice, which leads to macrophage necroptosis and increased mortality. Our findings also suggest that young alcoholic LTBI+ individuals have a higher risk of developing active TB infection. Author summary Chronic alcohol consumption modulates the host immune defense mechanism(s) and makes the host susceptible to various fungal, viral and bacterial infections, including Mycobacterium tuberculosis (Mtb). However, limited information is available about the mechanisms involved in alcohol-mediated host susceptibility to Mtb and other intracellular bacterial infections. In the current study, we fed control and alcohol diets to young and old mice and determined the mortality rates and the immune mechanisms involved in host susceptibility to Mtb infection. We found that alcohol increases the mortality of young mice but not old mice infected with Mtb. The increased mortality in alcohol-fed Mtb-infected young mice was due to IFN-α production by CD11b+Ly6G+ cells. We also found that PBMCs from young alcoholic individuals with latent tuberculosis infection (LTBI) produced significantly higher amounts of IFN-α than those from young non-alcoholic, old alcoholic and old non-alcoholic LTBI+ individuals. Our findings suggest that young alcoholic LTBI+ individuals have a higher risk of developing active TB infection. Our studies provide the first evidence that chronic alcohol consumption induces IFN-α production in young Mtb-infected mice and increases their mortality rates. Further characterization of CD11b+Ly6G+ cells and delineation of the mechanisms through which alcohol enhances IFN-α production in Ly6G+ cells during Mtb infection will facilitate the development of therapies for alcoholic individuals with latent and active Mtb. |
| Databáze: | OpenAIRE |
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