The macrophage mannose receptor induces IL-17 in response to Candida albicans.
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.
van de Veerdonk
Frank L
FL
Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Marijnissen
Renoud J
RJ
Kullberg
Bart Jan
BJ
Koenen
Hans J P M
HJ
Cheng
Shih-Chin
SC
Joosten
Irma
I
van den Berg
Wim B
WB
Williams
David L
DL
van der Meer
Jos W M
JW
Joosten
Leo A B
LA
Netea
Mihai G
MG
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
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