Dectin-1 mediates the biological effects of β-glucans

GD Brown, J Herre, DL Williams, JA Willment… - The Journal of …, 2003 - rupress.org
The Journal of experimental medicine, 2003rupress.org
The ability of fungal-derived β-glucan particles to induce leukocyte activation and the
production of inflammatory mediators, such as tumor necrosis factor (TNF)-α, is a well
characterized phenomenon. Although efforts have been made to understand how these
carbohydrate polymers exert their immunomodulatory effects, the receptors involved in
generating these responses are unknown. Here we show that Dectin-1 mediates the
production of TNF-α in response to zymosan and live fungal pathogens, an activity that …
The ability of fungal-derived β-glucan particles to induce leukocyte activation and the production of inflammatory mediators, such as tumor necrosis factor (TNF)-α, is a well characterized phenomenon. Although efforts have been made to understand how these carbohydrate polymers exert their immunomodulatory effects, the receptors involved in generating these responses are unknown. Here we show that Dectin-1 mediates the production of TNF-α in response to zymosan and live fungal pathogens, an activity that occurs at the cell surface and requires the cytoplasmic tail and immunoreceptor tyrosine activation motif of Dectin-1 as well as Toll-like receptor (TLR)-2 and Myd88. This is the first demonstration that the inflammatory response to pathogens requires recognition by a specific receptor in addition to the TLRs. Furthermore, these studies implicate Dectin-1 in the production of TNF-α in response to fungi, a critical step required for the successful control of these pathogens.
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