Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors
Mihai G. Netea, … , Alistair J.P. Brown, Bart Jan Kullberg
Mihai G. Netea, … , Alistair J.P. Brown, Bart Jan Kullberg
Published June 1, 2006
Citation Information: J Clin Invest. 2006;116(6):1642-1650. https://doi.org/10.1172/JCI27114.
View: Text | PDF
Research Article Microbiology

Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors

Abstract

The fungal pathogen Candida albicans has a multilayered cell wall composed of an outer layer of proteins glycosylated with N- or O-linked mannosyl residues and an inner skeletal layer of β-glucans and chitin. We demonstrate that cytokine production by human mononuclear cells or murine macrophages was markedly reduced when stimulated by C. albicans mutants defective in mannosylation. Recognition of mannosyl residues was mediated by mannose receptor binding to N-linked mannosyl residues and by TLR4 binding to O-linked mannosyl residues. Residual cytokine production was mediated by recognition of β-glucan by the dectin-1/TLR2 receptor complex. C. albicans mutants with a cell wall defective in mannosyl residues were less virulent in experimental disseminated candidiasis and elicited reduced cytokine production in vivo. We concluded that recognition of C. albicans by monocytes/macrophages is mediated by 3 recognition systems of differing importance, each of which senses specific layers of the C. albicans cell wall.

Authors

Mihai G. Netea, Neil A.R. Gow, Carol A. Munro, Steven Bates, Claire Collins, Gerben Ferwerda, Richard P. Hobson, Gwyneth Bertram, H. Bleddyn Hughes, Trees Jansen, Liesbeth Jacobs, Ed T. Buurman, Karlijn Gijzen, David L. Williams, Ruurd Torensma, Alistair McKinnon, Donna M. MacCallum, Frank C. Odds, Jos W.M. Van der Meer, Alistair J.P. Brown, Bart Jan Kullberg

×

Figure 6

The role of β-glucan/dectin-1 interaction for cytokine stimulation by C. albicans .

Options: View larger image (or click on image) Download as PowerPoint
The role of β-glucan/dectin-1 interaction for cytokin...
The role of β-glucan/dectin-1 interaction for C. albicans–induced TNF was investigated using 2 approaches with combinations of mutant C. albicans strains and receptor blockade: (A) stimulation with the och1 NGY357 strain (29) in TLR4–/– mice and (B) stimulation with mnt1 mnt2 NGY337 strain (27) in the presence of anti-MR antibodies in human MNCs. In both situations, the signals induced by N-linked mannosyl/MR and O-linked mannosyl/TLR4 complexes were deficient. The residual cytokine production stimulated by C. albicans in these 2 experimental conditions was completely blocked by laminarin, a ligand of dectin-1. Results (mean ± SD) are pooled data from 2 separate experiments with a total of 10 mice per group (A) or 8 human volunteers (B). *P < 0.05; **P < 0.01; ***P < 0.001 versus wild-type.