Sunday, July 16, 2006

How The Body Recognizes A Fungus Among Us

The fungus Candida albicans can cause a wide variety of infections, ranging from mucosal infections in generally healthy individuals to life-threatening infections in persons with impaired immunity. Beating this infection requires mononuclear immune cells such as neutrophils and macrophages to recognize the fungus, ingest it, and kill it by releasing proinflammatory cytokines that activate the immune response. In a study appearing online on May 18 in advance of print publication in the June issue of the Journal of Clinical Investigation, Mihai Netea and colleagues from Radboud University Nijmegen Medical Center, The Netherlands, show how mononuclear cells recognize the cell surface of C. albicans.

They reveal that this process involves multiple recognition systems that recognize various components within the layers of the fungal cell wall. The authors examined mutant strains of C. albicans that had specific defects in the mannosylation of cell wall proteins. They demonstrated that 3 components of the fungal cell wall are involved in the recognition by monocytes/macrophages and for the subsequent activation of proinflammatory cytokine release:

(i) N-linked mannans;

(ii) O-linked mannans; and

(iii) beta-glucans. The N-linked and O-linked mannosyl groups of glycoproteins of the outer surface of the cell wall were responsible for most of the cytokine-stimulating activity of the fungal cell. This was achieved by specific interaction of the N-linked mannosyl residues with the mannose receptor, and of the O-linked mannosyl residues with Toll-like receptor 4. Residual cytokine production was mediated by beta-glucans interacting with a protein called dectin-1, and most likely in cooperation with Toll-like receptor 2. This study will serve as a model for future studies of how the immune system recognizes other microorganisms.

TITLE: Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors.
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Journal of Clinical Investigation

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