Reprogramming of the macrophage transcriptome in response to interferon-γ and mycobacterium tuberculosis: Signaling roles of nitric oxide synthase-2 and phagocyte oxidase

Ehrt, S., Schnappinger, D., Bekiranov, S., Drenkow, J., Shi, S., Gingeras, T. R., Gaasterland, T., Schoolnik, G., Nathan, C. (2001) Reprogramming of the macrophage transcriptome in response to interferon-γ and mycobacterium tuberculosis: Signaling roles of nitric oxide synthase-2 and phagocyte oxidase. Journal of Experimental Medicine, 194 (8). pp. 1123-1139. ISSN 00221007 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/11602641
DOI: 10.1084/jem.194.8.1123

Abstract

Macrophage activation determines the outcome of infection by Mycobacterium tuberculosis (Mtb). Interferon-γ (IFN-γ) 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-γ and/or Mtb led to altered expression of 25% of the monitored genome in macrophages. The number of genes suppressed by IFN-γ 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-γ 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.

Item Type: Paper
Uncontrolled Keywords: Gene expression Innate immunity Macrophage activation Microarray analysis Phagocytosis gamma interferon Janus kinase nitric oxide synthase oxidoreductase phagocyte oxidase unclassified drug animal cell article controlled study gene repression immunity inflammation macrophage mouse Mycobacterium tuberculosis nonhuman priority journal signal transduction transcription regulation translation regulation Animals Gene Expression Regulation Interferon Type II Macrophages Membrane Glycoproteins Mice Mice Inbred C57BL Mice Knockout NADPH Oxidase Nitric Oxide Synthase Type II Oligonucleotide Array Sequence Analysis Phagocytes Reproducibility of Results Transcription Genetic
Subjects: organism description > bacteria
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > macrophages
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > macrophages
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > macrophages
CSHL Authors:
Communities: CSHL labs > Gingeras lab
Depositing User: CSHL Librarian
Date: 2001
Date Deposited: 13 Mar 2012 15:23
Last Modified: 15 Jul 2013 16:51
PMCID: PMC2193509
Related URLs:
URI: http://repository.cshl.edu/id/eprint/25281

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving