SWI/SNF Complex-mediated Chromatin Remodeling in Promotes Immune Evasion

Immune evasion is critical for fungal virulence. However, how the human opportunistic pathogen () accomplishes this is unknown. Here, we present the first genome-wide nucleosome map of the macrophage-internalized consisting of ∼12,000 dynamic and 70,000 total nucleosomes. We demonstrate that CgSnf2 (SWI/SNF chromatin remodeling complex-ATPase subunit)-mediated chromatin reorganization in macrophage-internalized upregulates and downregulates the immunosuppressive seven-gene mannosyltransferase-cluster () and immunostimulatory cell surface adhesin-encoding gene, respectively. Consistently, overexpression and deletion elevated IL-1β (pro-inflammatory cytokine) production and diminished proliferation in macrophages. Further, had higher Epa1 surface expression, and evoked increased IL-1β secretion, and was killed in macrophages. Akt-, p38-, NF-κB- or NLRP3 inflammasome-inhibition partially reversed increased IL-1β secretion in -infected macrophages. Importantly, macrophages responded to multiple pathogens via NF-κB-dependent IL-1β production, underscoring NF-κB signaling's role in fungal diseases. Altogether, our findings directly link the nucleosome positioning-based chromatin remodeling to fungal immunomodulatory molecule expression.