Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation
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- Eliseo F. Castillo
- Departments of aMolecular Genetics and Microbiology and
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- Alexander Dekonenko
- Internal Medicine and
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- John Arko-Mensah
- Departments of aMolecular Genetics and Microbiology and
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- Michael A. Mandell
- Departments of aMolecular Genetics and Microbiology and
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- Nicolas Dupont
- Departments of aMolecular Genetics and Microbiology and
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- Shanya Jiang
- Departments of aMolecular Genetics and Microbiology and
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- Monica Delgado-Vargas
- Departments of aMolecular Genetics and Microbiology and
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- Graham S. Timmins
- College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131;
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- Dhruva Bhattacharya
- Departments of aMolecular Genetics and Microbiology and
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- Hongliang Yang
- Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 805235; and
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- Julie Hutt
- Experimental Toxicology Division, Lovelace Respiratory Research Institute, Albuquerque, NM 87108
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- C. Rick Lyons
- Internal Medicine and
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- Karen M. Dobos
- Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 805235; and
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- Vojo Deretic
- Departments of aMolecular Genetics and Microbiology and
Abstract
<jats:p> Autophagy is a cell biological pathway affecting immune responses. In vitro, autophagy acts as a cell-autonomous defense against <jats:italic>Mycobacterium tuberculosis</jats:italic> , but its role in vivo is unknown. Here we show that autophagy plays a dual role against tuberculosis: antibacterial and anti-inflammatory. <jats:italic>M</jats:italic> . <jats:italic>tuberculosis</jats:italic> infection of Atg5 <jats:sup>fl/fl</jats:sup> LysM-Cre <jats:sup>+</jats:sup> mice relative to autophagy-proficient littermates resulted in increased bacillary burden and excessive pulmonary inflammation characterized by neutrophil infiltration and IL-17 response with increased IL-1α levels. Macrophages from uninfected Atg5 <jats:sup>fl/fl</jats:sup> LysM-Cre <jats:sup>+</jats:sup> mice displayed a cell-autonomous IL-1α hypersecretion phenotype, whereas T cells showed propensity toward IL-17 polarization during nonspecific activation or upon restimulation with mycobacterial antigens. Thus, autophagy acts in vivo by suppressing both <jats:italic>M</jats:italic> . <jats:italic>tuberculosis</jats:italic> growth and damaging inflammation. </jats:p>
Journal
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 109 (46), 3168-, 2012-10-23
Proceedings of the National Academy of Sciences
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Details 詳細情報について
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- CRID
- 1361699993354228096
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- ISSN
- 10916490
- 00278424
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- Data Source
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- Crossref