Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 194, Issue 8, Pages 1123-1139Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.194.8.1123
Keywords
gene expression; microarray analysis; macrophage activation; innate immunity; phagocytosis
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Funding
- NHLBI NIH HHS [HL61241-02] Funding Source: Medline
- NIAID NIH HHS [AI44826] Funding Source: Medline
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Macrophage activation determines the outcome of infection by Mycobacterium tuberculosis (Mtb). Interferon-gamma (IFN-gamma) activates macrophages by driving Janus tyrosine kinase (JAK)/signal transducer and activator of transcription-dependent induction of transcription and PKR-dependent suppression of translation. Microarray-based experiments reported here enlarge this picture. Exposure to IFN-gamma and/or Mtb led to altered expression of 25% of the monitored genome in macrophages. The number of genes suppressed by IFN-gamma exceeded the number of genes induced, and much of the suppression was transcriptional. Five times as many genes related to immunity and inflammation were induced than suppressed. Mtb mimicked or synergized with IFN-gamma more than antagonized its actions. Phagocytosis of nonviable Mtb or polystyrene beads affected many genes, but the transcriptional signature of macrophages infected with viable Mtb was distinct. Studies involving macrophages deficient in inducible nitric oxide synthase and/or phagocyte oxidase revealed that these two antimicrobial enzymes help orchestrate the profound transcriptional remodeling that underlies macrophage activation.
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