title: Similar inflammatory DC maturation signatures induced by TNF or Trypanosoma brucei antigens instruct default Th2-cell responses.
abstract: DCs represent the major cell type leading to polarized T-helper (Th) cell responses in vivo. Here, we asked whether the instruction of murine Th2 responses by DCs matured with the proinflammatory cytokine TNF is qualitatively different from maturation by different types of TLR4/MyD88-dependent variant-specific surface glycoproteins (VSGs) of Trypanosoma brucei (T. brucei). The results obtained by analyzing DC surface markers, Notch ligand mRNA, cytokines, asthma, and experimental autoimmune encephalomyelitis (EAE) models as well as performing microarrays indicate that both types of stimuli induce similar inflammatory, semi-mature DC profiles. DCs matured by TNF or VSG treatment expressed a common inflammatory signature of 24 genes correlating with their Th2-polarization capacity. However, the same 24 genes and 4498 additional genes were expressed by DCs treated with LPS that went on to induce Th1 cells. These findings support the concept of a default pathway for Th2-cell induction in DCs matured under suboptimal or inflammatory conditions, independent of the surface receptors and signaling pathways involved. Our data also indicate that quantitative differences in DC maturation might direct Th2- vs Th1-cell responses, since suboptimally matured inflammatory DCs induce default Th2-cell maturation, whereas fully mature DCs induce Th1-cell maturation.
authors.affiliation: Institute of Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Katrien
authors.initials: K
authors.lastname: Pletinckx
authors.forename: Benoit
authors.initials: B
authors.lastname: Stijlemans
authors.forename: Vladimir
authors.initials: V
authors.lastname: Pavlovic
authors.forename: Regina
authors.initials: R
authors.lastname: Laube
authors.forename: Carolin
authors.initials: C
authors.lastname: Brandl
authors.forename: Susanne
authors.initials: S
authors.lastname: Kneitz
authors.forename: Alain
authors.initials: A
authors.lastname: Beschin
authors.forename: Patrick
authors.initials: P
authors.lastname: De Baetselier
authors.forename: Manfred B
authors.initials: MB
authors.lastname: Lutz
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D007249:Inflammation / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014346:Trypanosoma brucei brucei / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000276:immunology* / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D014643:Variant Surface Glycoproteins, Trypanosoma