Transcriptome analysis of murine macrophages in response to infection with Streptococcus pyogenes reveals an unusual activation program.

2.50
Hdl Handle:
http://hdl.handle.net/10033/19532
Title:
Transcriptome analysis of murine macrophages in response to infection with Streptococcus pyogenes reveals an unusual activation program.
Authors:
Goldmann, Oliver; von Köckritz-Blickwede, Maren; Höltje, Claudia; Chhatwal, Gursharan S; Geffers, Robert; Medina, Eva ( 0000-0001-9073-0223 )
Abstract:
The complex response of murine macrophages to infection with Streptococcus pyogenes was investigated at the level of gene expression with a high-density oligomer microarray. More than 400 genes were identified as being differentially regulated. Many of the up-regulated genes encode molecules involved in the immune response and in inflammation, transcription, signaling, apoptosis, the cell cycle, electron transport, and cell adhesion. Of particular interest was the up-regulation of proinflammatory cytokines, typical of the classically activated macrophages (M1 phenotype), such as tumor necrosis factor alpha, interleukin 1 (IL-1), and IL-6, and as well as the up-regulation of anti-inflammatory mediators, such as IL-1 decoy receptor and IL-10, associated with alternative macrophage activation (M2 phenotype). Furthermore, the gene encoding inducible nitric oxide synthase (iNOS), an enzyme typically implicated in classical activation, was not induced in infected macrophages. Instead, the gene encoding arginase, a competitor for the iNOS substrate arginine involved in the alternative activation pathway, was up-regulated in S. pyogenes-infected cells. Thus, the microarray-based gene expression analysis demonstrated that S. pyogenes induces an atypical activation program in macrophages, with some but not all features of the classical or alternative activation phenotypes. The microarray data also suggested that the bactericidal activity of macrophages against S. pyogenes is mediated by phagocyte oxidase, as p47phox was up-regulated in infected cells. Indeed, the in vivo and in vitro killing of S. pyogenes was markedly diminished in the absence of functional phagocyte (p47(phox-/-)) but not in the absence of iNOS (iNOS(-/-)). An understanding of how macrophages respond to S. pyogenes at the molecular level may facilitate the development of new therapeutic paradigms.
Affiliation:
Infection Immunology Research Group, Helmholtz Center for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
Citation:
Transcriptome analysis of murine macrophages in response to infection with Streptococcus pyogenes reveals an unusual activation program. 2007, 75 (8):4148-57 Infect. Immun.
Journal:
Infection and immunity
Issue Date:
Aug-2007
URI:
http://hdl.handle.net/10033/19532
DOI:
10.1128/IAI.00181-07
PubMed ID:
17526748
Type:
Article
Language:
en
ISSN:
0019-9567
Appears in Collections:
publications of the research group immunology of infection (INI)

Full metadata record

DC FieldValue Language
dc.contributor.authorGoldmann, Oliveren
dc.contributor.authorvon Köckritz-Blickwede, Marenen
dc.contributor.authorHöltje, Claudiaen
dc.contributor.authorChhatwal, Gursharan Sen
dc.contributor.authorGeffers, Roberten
dc.contributor.authorMedina, Evaen
dc.date.accessioned2008-03-03T13:32:53Zen
dc.date.available2008-03-03T13:32:53Zen
dc.date.issued2007-08en
dc.identifier.citationTranscriptome analysis of murine macrophages in response to infection with Streptococcus pyogenes reveals an unusual activation program. 2007, 75 (8):4148-57 Infect. Immun.en
dc.identifier.issn0019-9567en
dc.identifier.pmid17526748en
dc.identifier.doi10.1128/IAI.00181-07en
dc.identifier.urihttp://hdl.handle.net/10033/19532en
dc.description.abstractThe complex response of murine macrophages to infection with Streptococcus pyogenes was investigated at the level of gene expression with a high-density oligomer microarray. More than 400 genes were identified as being differentially regulated. Many of the up-regulated genes encode molecules involved in the immune response and in inflammation, transcription, signaling, apoptosis, the cell cycle, electron transport, and cell adhesion. Of particular interest was the up-regulation of proinflammatory cytokines, typical of the classically activated macrophages (M1 phenotype), such as tumor necrosis factor alpha, interleukin 1 (IL-1), and IL-6, and as well as the up-regulation of anti-inflammatory mediators, such as IL-1 decoy receptor and IL-10, associated with alternative macrophage activation (M2 phenotype). Furthermore, the gene encoding inducible nitric oxide synthase (iNOS), an enzyme typically implicated in classical activation, was not induced in infected macrophages. Instead, the gene encoding arginase, a competitor for the iNOS substrate arginine involved in the alternative activation pathway, was up-regulated in S. pyogenes-infected cells. Thus, the microarray-based gene expression analysis demonstrated that S. pyogenes induces an atypical activation program in macrophages, with some but not all features of the classical or alternative activation phenotypes. The microarray data also suggested that the bactericidal activity of macrophages against S. pyogenes is mediated by phagocyte oxidase, as p47phox was up-regulated in infected cells. Indeed, the in vivo and in vitro killing of S. pyogenes was markedly diminished in the absence of functional phagocyte (p47(phox-/-)) but not in the absence of iNOS (iNOS(-/-)). An understanding of how macrophages respond to S. pyogenes at the molecular level may facilitate the development of new therapeutic paradigms.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshBALB 3T3 Cellsen
dc.subject.meshColony Count, Microbialen
dc.subject.meshCytokinesen
dc.subject.meshFemaleen
dc.subject.meshGene Expression Profilingen
dc.subject.meshGene Expression Regulationen
dc.subject.meshMacrophage Activationen
dc.subject.meshMacrophages, Peritonealen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C3Hen
dc.subject.meshMice, Knockouten
dc.subject.meshMicrobial Viabilityen
dc.subject.meshModels, Animalen
dc.subject.meshNADPH Oxidaseen
dc.subject.meshOligonucleotide Array Sequence Analysisen
dc.subject.meshStreptococcus pyogenesen
dc.subject.meshUp-Regulationen
dc.titleTranscriptome analysis of murine macrophages in response to infection with Streptococcus pyogenes reveals an unusual activation program.en
dc.typeArticleen
dc.contributor.departmentInfection Immunology Research Group, Helmholtz Center for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.en
dc.identifier.journalInfection and immunityen

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