title: The macrophage mannose receptor induces IL-17 in response to Candida albicans.
abstract: The cytokine IL-17 controls neutrophil-mediated inflammatory responses. The pattern recognition receptor(s) that induce Th17 responses during infection, in the absence of artificial mitogenic stimulation with anti-CD3/anti-CD28 antibodies, remain obscure. We investigated the innate immune receptors and pathogen-associated molecular patterns involved in triggering Th17 responses during pathogen-specific host defense. The prototypic fungal pathogen Candida albicans was found to induce IL-17 more potently than Gram-negative bacteria. Candida mannan, but not zymosan, beta-glucans, Toll-like receptor (TLR) agonists, or the NOD2 ligand MDP, induced IL-17 production in the absence of anti-CD3/anti-CD28 antibodies. Candida-induced IL-17 response was dependent on antigen-presenting cells and the macrophage mannose receptor (MR), demonstrating that Candida mannan is not simply a mitogenic stimulus. The TLR2/dectin-1 pathway, but not TLR4 or NOD2, amplified MR-induced IL-17 production. This study identifies the specific pattern recognition receptors that trigger the Th17 response induced by a human pathogen in the absence of mitogenic stimulation.
authors.affiliation: Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Frank L
authors.initials: FL
authors.lastname: van de Veerdonk
authors.forename: Renoud J
authors.initials: RJ
authors.lastname: Marijnissen
authors.forename: Bart Jan
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: Hans J P M
authors.initials: HJ
authors.lastname: Koenen
authors.forename: Shih-Chin
authors.initials: SC
authors.lastname: Cheng
authors.forename: Irma
authors.initials: I
authors.lastname: Joosten
authors.forename: Wim B
authors.initials: WB
authors.lastname: van den Berg
authors.forename: David L
authors.initials: DL
authors.lastname: Williams
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
mesh_terms: D002176:Candida albicans / Q000276:immunology*; D002473:Cell Wall / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis*; D037181:Lectins, C-Type / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008351:Mannans / Q000276:immunology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology; D000099181:Dectin-1
chemical_list: D020381:Interleukin-17; D037181:Lectins, C-Type; D008351:Mannans; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D000099181:Dectin-1; C495342:TLR2 protein, human