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Статья
Irg1 expression in myeloid cells prevents immunopathology during M. tuberculosis infection
2021
Immune-Responsive Gene 1 (Irg1) is a mitochondrial enzyme that produces itaconate under inflammatory conditions, principally in cells of myeloid lineage. Cell culture studies suggest that itaconate regulates inflammation through its inhibitory effects on cytokine and reactive oxygen species production. To evaluate the functions of Irg1 in vivo, we challenged wild-type (WT) and Irg1-/- mice with Mycobacterium tuberculosis (Mtb) and monitored disease progression. Irg1-/-, but not WT, mice succumbed rapidly to Mtb, and mortality was associated with increased infection, inflammation, and pathology. Infection of LysM-Cre Irg1fl/fl, Mrp8-Cre Irg1fl/fl, and CD11c-Cre Irg1fl/fl conditional knockout mice along with neutrophil depletion experiments revealed a role for Irg1 in LysM+ myeloid cells in preventing neutrophil-mediated immunopathology and disease. RNA sequencing analyses suggest that Irg1 and its production of itaconate temper Mtb-induced inflammatory responses in myeloid cells at the transcriptional level. Thus, an Irg1 regulatory axis modulates inflammation to curtail Mtb-induced lung disease. © 2018 Nair et al.
Цитирование
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Версии
- 1. Version of Record от 2021-04-27
Метаданные
Название журнала
- Journal of Experimental Medicine
Том
- 215
Выпуск
- 4
Страницы
- 1035-1045
Ключевые слова
- CXCL1 chemokine; gamma interferon; granulocyte colony stimulating factor; interleukin 12p70; interleukin 17; interleukin 1beta; interleukin 6; itaconic acid; macrophage inflammatory protein 1alpha; macrophage inflammatory protein 1beta; monocyte chemotactic protein 1; tumor necrosis factor; cytokine; hydrolyase; Irg1 protein, mouse; reactive oxygen metabolite; succinic acid derivative; animal cell; animal experiment; animal model; animal tissue; Article; bone marrow cell; controlled study; cytokine release; dendritic cell; disease exacerbation; eosinophil; female; gene expression; immune responsive gene 1; immunopathology; inflammation; knockout mouse; lung alveolus macrophage; lung tuberculosis; male; mitochondrial gene; monocyte; mortality; mouse; Mycobacterium tuberculosis; natural killer cell; natural killer T cell; neutrophil; nonhuman; priority journal; RNA sequence; wild type mouse; animal; bone marrow cell; C57BL mouse; gene expression; genetic transcription; immunology; lung disease; metabolism; microbiology; tuberculosis; Animals; Cytokines; Disease Progression; Female; Gene Expression; Hydro-Lyases; Inflammation; Lung Diseases; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mycobacterium tuberculosis; Myeloid Cells; Neutrophils; Reactive Oxygen Species; Succinates; Transcription, Genetic; Tuberculosis
Издатель
- Rockefeller University Press
Тип документа
- journal article
Тип лицензии Creative Commons
- CC
Правовой статус документа
- Свободная лицензия
Источник
- scopus
