Dectin-1 Mediates the Biological Effects of β-Glucans

By Gordon D. Brown, J. Herre, David L. Williams, J. Willment, Andrew J. Marshall, S. Gordon. Journal of Experimental Medicine, 2003

1,197 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Infectious Diseases, Plant Science

View Paper: https://www.semanticscholar.org/paper/2a9cf2cba1addbe8eedf4560b9bf61b2984885d5

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. Mihai G. Netea
2. Gordon D. Brown
3. N. Gow
4. R. Steinman
5. H. Hemmi

In Infectious Diseases

1. Gordon D. Brown
2. Mihai G. Netea
3. N. Gow

In Plant Science

1. Gordon D. Brown
2. Mihai G. Netea
3. N. Gow

Citations in the corpus

• DC-SIGN: escape mechanism for pathogens (2003, background): “The function of these activating or inhibitory signalling motifs is not yet clear, but the finding that pathogen recognition by lectins, such as DC-SIGN, inhibits intracellular signalling processes that are initiated by TLR activatio”
• Dendritic cells: translating innate to adaptive immunity. (2006, background): “and DCs, binds yeast or zymosan particles but, in addition, dectin-1 associates with TLR-2 and thereby signals TNF-α and IL-12 production [86, 87].”
• An integrated model of the recognition of Candida albicans by the innate immune system (2008, background): “Although Syk-dependent signalling from dectin 1 is sufficient for these responses, stimulation of the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB pathways, with subsequent production of pro-inflammatory cytokines, such as tumour necrosis factor (TNF), requires collaborative si”
• Toll-Like Receptor 2 Suppresses Immunity against Candida albicans through Induction of IL-10 and Regulatory T Cells (2004, background): “albicans (22, 23), and it is tempting to speculate on the role of -glucan receptors in the findings described in this work.”
• Dectin‐1 mediates macrophage recognition of Candida albicans yeast but not filaments (2005, background): “Dectin-1 is expressed widely on phagocytes including macrophages and dendritic cells and contributes to the immunological response to b-glucans (Brown and Gordon, 2003).”