Transcriptome analysis of murine macrophages in response to infection with Streptococcus pyogenes reveals an unusual activation program.
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Authors
Goldmann, Olivervon Köckritz-Blickwede, Maren
Höltje, Claudia
Chhatwal, Gursharan S
Geffers, Robert
Medina, Eva
Issue Date
2007-08
Metadata
Show full item recordAbstract
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.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.Affiliation
Infection Immunology Research Group, Helmholtz Center for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.Journal
Infection and immunityPubMed ID
17526748Type
ArticleLanguage
enISSN
0019-9567ae974a485f413a2113503eed53cd6c53
10.1128/IAI.00181-07
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