title: Receptor recognition of and immune intracellular pathways for Veillonella parvula lipopolysaccharide.
abstract: Veillonella parvula is an anaerobic gram-negative coccus that is part of the normal flora of the animal and human mouth and gastrointestinal and genitourinary tracts. Oral V. parvula is involved in the development of early periodontal disease as well as different types of serious infections. Present data on molecular mechanisms responsible for innate immune response against Veillonella are very scanty. The aim of this study was to investigate the Toll-like receptor (TLR) pathways responsible for V. parvula lipopolysaccharide (LPS) and to identify the intracellular pathways induced by this recognition. V. parvula LPS stimulated tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) release in human peripheral blood mononuclear cells (PBMC) in a dose-dependent manner. Pretreatment of cells with a TLR4 antagonist significantly reduced TNF-alpha and IL-6 production in PBMC stimulated with either Veillonella or Escherichia coli LPS. However, V. parvula LPS was 10- to 100-fold less active than E. coli LPS for cytokine induction. TNF-alpha, IL-1beta, IL-6, and IL-10 were released in wild-type and TLR2(-/-), but not TLR4(-/-), mouse macrophage cultures. V. parvula LPS was able to activate the human PBMC p38 mitogen-activated protein kinase (MAPK). A specific p38 MAPK inhibitor strongly inhibited V. parvula LPS-induced TNF-alpha, IL-1beta, IL-6, and IL-10. In conclusion, V. parvula LPS is able to induce cytokine production in both human and murine in vitro models, although it is less effective than Enterobacteriaceae LPS. V. parvula LPS-stimulated cytokine induction, as well as p38 MAPK activation, are TLR4-dependent features.
authors.affiliation: Institute of Microbiology, Department of Medical Sciences, University of Cantanzaro, Catanzaro, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Matera
authors.forename: Valentina
authors.initials: V
authors.lastname: Muto
authors.forename: Maria
authors.initials: M
authors.lastname: Vinci
authors.forename: Emilia
authors.initials: E
authors.lastname: Zicca
authors.forename: Shahla
authors.initials: S
authors.lastname: Abdollahi-Roodsaz
authors.forename: Frank L
authors.initials: FL
authors.lastname: van de Veerdonk
authors.forename: Bart-Jan
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Liberto
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
authors.forename: Alfredo
authors.initials: A
authors.lastname: Focà
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
mesh_terms: D000818:Animals; D018413:Bartonella quintana / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D014678:Veillonella / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: C508609:IL10 protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D048051:p38 Mitogen-Activated Protein Kinases