SWI/SNF complex-mediated chromatin remodeling in Candida glabrata promotes immune evasion
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 nucleosom...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224008290 |
| _version_ | 1827287912481292288 |
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| author | Kundan Kumar Aditi Pareek Rupinder Kaur |
| author_facet | Kundan Kumar Aditi Pareek Rupinder Kaur |
| author_sort | Kundan Kumar |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T11:20:46Z |
| format | Article |
| id | doaj.art-1ea7c4024a1448ff94915954e51451b0 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-24T11:20:46Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-1ea7c4024a1448ff94915954e51451b02024-04-11T04:41:48ZengElsevieriScience2589-00422024-04-01274109607SWI/SNF complex-mediated chromatin remodeling in Candida glabrata promotes immune evasionKundan Kumar0Aditi Pareek1Rupinder Kaur2Laboratory of Fungal Pathogenesis, Centre for DNA Fingerprinting and Diagnostics, Hyderabad 500039, IndiaLaboratory of Fungal Pathogenesis, Centre for DNA Fingerprinting and Diagnostics, Hyderabad 500039, India; Graduate studies, Manipal Academy of Higher Education, Manipal, Karnataka 576104, IndiaLaboratory of Fungal Pathogenesis, Centre for DNA Fingerprinting and Diagnostics, Hyderabad 500039, India; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004224008290Biological sciencesMolecular biologyImmunologyMicrobiologyMycology |
| spellingShingle | Kundan Kumar Aditi Pareek Rupinder Kaur SWI/SNF complex-mediated chromatin remodeling in Candida glabrata promotes immune evasion iScience Biological sciences Molecular biology Immunology Microbiology Mycology |
| title | SWI/SNF complex-mediated chromatin remodeling in Candida glabrata promotes immune evasion |
| title_full | SWI/SNF complex-mediated chromatin remodeling in Candida glabrata promotes immune evasion |
| title_fullStr | SWI/SNF complex-mediated chromatin remodeling in Candida glabrata promotes immune evasion |
| title_full_unstemmed | SWI/SNF complex-mediated chromatin remodeling in Candida glabrata promotes immune evasion |
| title_short | SWI/SNF complex-mediated chromatin remodeling in Candida glabrata promotes immune evasion |
| title_sort | swi snf complex mediated chromatin remodeling in candida glabrata promotes immune evasion |
| topic | Biological sciences Molecular biology Immunology Microbiology Mycology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224008290 |
| work_keys_str_mv | AT kundankumar swisnfcomplexmediatedchromatinremodelingincandidaglabratapromotesimmuneevasion AT aditipareek swisnfcomplexmediatedchromatinremodelingincandidaglabratapromotesimmuneevasion AT rupinderkaur swisnfcomplexmediatedchromatinremodelingincandidaglabratapromotesimmuneevasion |