SWI/SNF complex-mediated chromatin remodelling is vital for cell surface adhesin repression and immune evasion

Immune evasion is critical for fungal virulence. However, how the human opportunistic pathogen Candida glabrata ( Cg ) accomplishes this is unknown. Here, using micrococcal nuclease-sequencing, RNA-sequencing, macrophage-signalling and genetic analyses, we demonstrate that chromatin remodelling in macrophage-internalized Cg , via CgSnf2 [SWI/SNF chromatin remodelling complex-ATPase subunit], leads to transcriptional upregulation and downregulation of immunosuppressive seven-gene mannosyltransferase-cluster ( CgMT-C ) and immunostimulatory cell surface adhesin-encoding EPA1 gene, respectively. Consistently, EPA1 overexpression and CgMT-C deletion led to increased proinflammatory cytokine IL-1β production and reduced Cg proliferation in macrophages. Further, CgSNF2 deletion evoked increased IL-1β secretion, and the consequent killing of macrophage-internalized Cg , with elevated IL-1β levels reversed partially in Akt-, p38-, NF-κB- or NLRP3 inflammasome-inhibited macrophages. Importantly, macrophages respond to multiple Candida pathogens via NF-κB-dependent IL-1β production, underscoring NF-κB signalling role in fungal diseases. Altogether, our findings directly link nucleosome positioning-based chromatin remodelling to fungal immunomodulatory molecule expression, which dictates Cg fate in host immune cells. ### Competing Interest Statement The authors have declared no competing interest.