C1QBP interacts with Dectin-1 signaling to suppress IL-1β via epigenetic silencing in Candida albicans infection

Dectin-1-mediated interleukin-1β (IL-1β) production is critical for antifungal immunity, yet the transcriptional regulation of IL-1β during Candida albicans infection remain poorly defined. Here, we identify conventional type 2 dendritic cells (cDC2s) as the primary producers of IL-1β in the kidney during disseminated candidiasis and uncover Complement C1q binding protein (C1QBP; gC1qR/p32) as a key transcriptional repressor. Mechanistically, C1QBP constrains Dectin-1-driven IL-1β production by sequestering phosphorylated PKCδ (p-PKCδ) in the cytosol, thereby preventing its nuclear translocation. Genetic ablation of C1qbp relieved this sequestration, enabling nuclear p-PKCδ to directly activate the E3 ubiquitin ligase complex RNF20/RNF40. This complex in turn facilitated DOT1L-mediated histone H3 lysine 79 trimethylation (H3K79me3) across the Il1b gene body, epigenetically enhancing its transcription. Consequently, DC-specific C1QBP depletion elevated IL-1β production, amplified protective TH17 responses, and significantly improved host resistance to disseminated candidiasis. Collectively, our findings reveal C1QBP as a spatial rheostat for p-PKCδ that epigenetically silences Dectin-1-mediated inflammation, highlighting C1QBP as a therapeutic target to potentiate antifungal defense.