SWI/SNF complex-mediated chromatin remodeling in Candida glabrata promotes immune evasion
| Autor: | Kundan Kumar, Aditi Pareek, Rupinder Kaur |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | iScience, Vol 27, Iss 4, Pp 109607- (2024) |
| Druh dokumentu: | article |
| ISSN: | 2589-0042 94915954 |
| DOI: | 10.1016/j.isci.2024.109607 |
| Popis: | Summary: Immune evasion is critical for fungal virulence. However, how the human opportunistic pathogen Candida glabrata (Cg) accomplishes this is unknown. Here, we present the first genome-wide nucleosome map of the macrophage-internalized Cg 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 Cg upregulates and downregulates the immunosuppressive seven-gene mannosyltransferase-cluster (CgMT-C) and immunostimulatory cell surface adhesin-encoding EPA1 gene, respectively. Consistently, EPA1 overexpression and CgMT-C deletion elevated IL-1β (pro-inflammatory cytokine) production and diminished Cg proliferation in macrophages. Further, Cgsnf2Δ 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 Cgsnf2Δ-infected macrophages. Importantly, macrophages responded to multiple Candida 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. |
| Databáze: | Directory of Open Access Journals |
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