Reprogramming of the Macrophage Transcriptome in Response to Interferon-γ and <i>Mycobacterium tuberculosis</i>

Sabine Ehrt; Dirk Schnappinger; Stefan Bekiranov; Jörg Drenkow; Shuangping Shi; T Gingeras; Terry Gaasterland; Gary K. Schoolnik; Carl Nathan

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.

Keywords

BiologyMycobacterium tuberculosisInterferonJanus kinaseTranscriptomeSTAT proteinInflammationMacrophagePhagocytosisCell biologySTAT3MicrobiologyGene expressionTuberculosisGeneKinaseSignal transductionImmunologyGeneticsMedicine

MeSH Terms

AnimalsGene Expression RegulationInterferon-gammaMacrophage ActivationMacrophagesMembrane GlycoproteinsMiceMiceInbred C57BLMiceKnockoutMycobacterium tuberculosisNADPH Oxidase 2NADPH OxidasesNitric Oxide SynthaseNitric Oxide Synthase Type IIOligonucleotide Array Sequence AnalysisPhagocytesReproducibility of ResultsSignal TransductionTranscriptionGenetic

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Publication Info

Year: 2001
Type: article
Volume: 194
Issue: 8
Pages: 1123-1140
Citations: 459
Access: Closed

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APA Style

                            
                                
                                    Sabine Ehrt, 
                                
                                    Dirk Schnappinger, 
                                
                                    Stefan Bekiranov
                                
                                et al.
                            
                            (2001). 
                            Reprogramming of the Macrophage Transcriptome in Response to Interferon-γ and <i>Mycobacterium tuberculosis</i>. 
                            The Journal of Experimental Medicine
                            , 194
                            (8)
                            , 1123-1140.
                            https://doi.org/10.1084/jem.194.8.1123
                        

Identifiers

DOI: 10.1084/jem.194.8.1123
PMID: 11602641
PMCID: PMC2193509

Data Quality

Data completeness: 86%