Bates, Steven

Bertram, Gwyneth

Brown, Alistair James Petersen

Buurman, Ed T

Collins, Claire

Ferwerda, Gerben

Gijzen, Karlijn

Gow, Neil Andrew Robert

Hobson, Richard Patrick

Hughes, Huw Bleddyn

Jacobs, Liesbeth

Jansen, Trees

Kullberg, Bart Jan

MacCallum, Donna Margaret

McKinnon, Alistair

Munro, Carol Anne

Netea, Mihai G

Odds, Frank Christopher

Torensma, Ruurd

Van der Meer, Jos W.M.

Williams, David L.

Journal of Clinical Investigation

English

PubMed

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 beta-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 beta-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

Netea, M.G.

Gow, N.A.

Munro, C.A.

Bates, S.

Collins, C.

Ferwerda, G.

Hobson, R.P.

Bertram, G.

Hughes, H.B.

Jansen, T.

Jacobs, L.

Buurman, E.T.

Gijzen, K.

Williams, D.L.

Torensma, R.

McKinnon, A.

MacCallum, D.M.

Odds, F.C.

Meer, J.W.M. van der

Brown, A.

Kullberg, B.J.

NARCIS 

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

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

Netea, Mihai

Gow, Neil A.R.

Munro, Carol A.

Hobson, Richard P.

Hughes, H. Bleddyn

Buurman, Ed T.

MacCallum, Donna M.

Odds, Frank C.

Van Der Meer, Jos W.M.

Brown, Alistair J.P.

East Tennessee State University

Immune Sensing of Candida Albicans Requires Cooperative Recognition of Mannans and Glucans by Lectin and Toll-Like Receptors

Contains fulltext :
                  51330.pdf (publisher's version ) (Open Access)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 beta-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 beta-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

Radboud Repository

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1462942

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

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

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East Tennessee State University

Radboud Repository