title: TLR9-dependent and independent pathways drive activation of the immune system by Propionibacterium acnes.
abstract: Propionibacterium acnes is usually a relatively harmless commensal. However, under certain, poorly understood conditions it is implicated in the etiology of specific inflammatory diseases. In mice, P. acnes exhibits strong immunomodulatory activity leading to splenomegaly, intrahepatic granuloma formation, hypersensitivity to TLR ligands and endogenous cytokines, and enhanced resistance to infection. All these activities reach a maximum one week after P. acnes priming and require IFN-γ and TLR9. We report here the existence of a markedly delayed (1-2 weeks), but phenotypically similar TLR9-independent immunomodulatory response to P. acnes. This alternative immunomodulation is also IFN-γ dependent and requires functional MyD88. From our experiments, a role for MyD88 in the IFN-γ-mediated P. acnes effects seems unlikely and the participation of the known MyD88-dependent receptors, including TLR5, Unc93B-dependent TLRs, IL-1R and IL-18R in the development of the alternative response has been excluded. However, the crucial role of MyD88 can partly be attributed to TLR2 and TLR4 involvement. Either of these two TLRs, activated by bacteria and/or endogenously generated ligands, can fulfill the required function. Our findings hint at an innate immune sensitizing mechanism, which is potentially operative in both infectious and sterile inflammatory disorders.
authors: Department of Developmental Immunology, Max Planck Institute of Immunbiology und Epigenetics, Freiburg, Germany.
authors: Sandrine
authors: S
authors: Tchaptchet
authors: Marina
authors: M
authors: Gumenscheimer
authors: Christoph
authors: C
authors: Kalis
authors: Nikolaus
authors: N
authors: Freudenberg
authors: Christoph
authors: C
authors: Hölscher
authors: Carsten J
authors: CJ
authors: Kirschning
authors: Marinus
authors: M
authors: Lamers
authors: Chris
authors: C
authors: Galanos
authors: Marina A
authors: MA
authors: Freudenberg
mesh_terms: D000818:Animals; D007107:Immune System / Q000187:drug effects / Q000378:metabolism*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D011425:Propionibacterium acnes / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism; D053707:Receptors, Interleukin-12 / Q000235:genetics / Q000378:metabolism; D053724:Receptors, Interleukin-18 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013163:Splenomegaly / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D017472:Receptors, Interleukin-1; D053707:Receptors, Interleukin-12; D053724:Receptors, Interleukin-18; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma