Identification and structural characterization of soluble dectin-1 with β-glucan-binding activity in THP-1 cell culture supernatant

Abstract

Dectin-1, a major receptor in antifungal immunity, functions as membrane-bound Dectin-1 (mDectin-1). However, the biological functions of its soluble form, sDectin-1, remain poorly understood. In this study, we established a THP-1 cell line stably expressing human Dectin-1 A with N-terminal FLAG and C-terminal HiBiT tags to analyze the mechanism underlying the presence of sDectin-1 in the extracellular environment, its molecular form, and its capabilities. As a result, sDectin-1 was detected constitutively in the culture supernatant, but its level increased upon stimulation via the Dectin-1–Syk pathway (curdlan) and by Dectin-1-independent inflammatory signals (TNF-α). Functional analysis revealed that sDectin-1 retains its ligand-binding capacity to both insoluble and soluble β-glucans. Furthermore, western blotting suggested that the predominant molecular form of sDectin-1 is an N-terminally truncated fragment, consistent with the extracellular domain truncation. This study demonstrates that sDectin-1 is a functional, soluble receptor that retains ligand-binding capacity and whose level is regulated by inflammatory signals. This finding suggests that sDectin-1 may function as a decoy receptor or trans-signaling factor, providing new perspectives on antifungal immunity.