The study investigates the role of Dectin-1 in mediating the biological effects of β-glucans, specifically in inducing TNF-α production in response to zymosan and live fungal pathogens. Dectin-1, a β-glucan receptor, is shown to mediate this response at the cell surface, requiring its cytoplasmic tail and immunoreceptor tyrosine activation motif (ITAM) 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 TLRs. The findings suggest that Dectin-1 plays a crucial role in the innate immune response to fungal pathogens by facilitating the production of TNF-α, which is essential for controlling these infections.The study investigates the role of Dectin-1 in mediating the biological effects of β-glucans, specifically in inducing TNF-α production in response to zymosan and live fungal pathogens. Dectin-1, a β-glucan receptor, is shown to mediate this response at the cell surface, requiring its cytoplasmic tail and immunoreceptor tyrosine activation motif (ITAM) 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 TLRs. The findings suggest that Dectin-1 plays a crucial role in the innate immune response to fungal pathogens by facilitating the production of TNF-α, which is essential for controlling these infections.