{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhou T"],"funding":["U.S. Department of Health & Human Services | NIH | National Eye Institute","U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences","NEI NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)","U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)","NIGMS NIH HHS"],"pagination":["1562"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11821908"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["High-damaging Candida albicans strains tend to form hyphae and exacerbate intestinal inflammation in ulcerative colitis patients through IL-1β-dependent mechanisms. Fungal agglutinin-like sequence (Als) proteins worsen DSS-induced colitis in mouse models. FADD and caspase-8 are important regulators of gut homeostasis and inflammation. However, whether they link directly to fungal proteins is not fully understood. Here, we report that Als proteins induce IL-1β release in immune cells. We show that hyphal Als3 is internalized in macrophages and interacts with caspase-8 and the inflammasome adaptor apoptosis-associated speck-like protein containing a CARD (ASC). Caspase-8 is essential for Als3-mediated ASC oligomerization and IL-1β processing. In non-immune cells, Als3 is associated with cell death core components FADD and caspase-8. N-terminal Als3 (N-Als3) expressed in Jurkat cells partially inhibits apoptosis. Mechanistically, N-Als3 promotes oligomerization of FADD and caspase-8 through their death effector domains (DEDs). N-Als3 variants with a mutation in the peptide-binding cavity or amyloid-forming region are impaired in DED oligomerization. Together, these results demonstrate that DEDs are intracellular sensors of Als3. This study identifies additional potential targets to control hypha-induced inflammation."],"journal":["Nature communications"],"pubmed_title":["Fungal Als proteins hijack host death effector domains to promote inflammasome signaling."],"pmcid":["PMC11821908"],"funding_grant_id":["R01 EY036478","R01EY036478","R01 GM117111","R01GM117111"],"pubmed_authors":["Liu H","Marshall M","Solis NV","Filler SG","Zhou T","Yao Q","Pearlman E"],"additional_accession":[]},"is_claimable":false,"name":"Fungal Als proteins hijack host death effector domains to promote inflammasome signaling.","description":"High-damaging Candida albicans strains tend to form hyphae and exacerbate intestinal inflammation in ulcerative colitis patients through IL-1β-dependent mechanisms. Fungal agglutinin-like sequence (Als) proteins worsen DSS-induced colitis in mouse models. FADD and caspase-8 are important regulators of gut homeostasis and inflammation. However, whether they link directly to fungal proteins is not fully understood. Here, we report that Als proteins induce IL-1β release in immune cells. We show that hyphal Als3 is internalized in macrophages and interacts with caspase-8 and the inflammasome adaptor apoptosis-associated speck-like protein containing a CARD (ASC). Caspase-8 is essential for Als3-mediated ASC oligomerization and IL-1β processing. In non-immune cells, Als3 is associated with cell death core components FADD and caspase-8. N-terminal Als3 (N-Als3) expressed in Jurkat cells partially inhibits apoptosis. Mechanistically, N-Als3 promotes oligomerization of FADD and caspase-8 through their death effector domains (DEDs). N-Als3 variants with a mutation in the peptide-binding cavity or amyloid-forming region are impaired in DED oligomerization. Together, these results demonstrate that DEDs are intracellular sensors of Als3. This study identifies additional potential targets to control hypha-induced inflammation.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Feb","modification":"2026-05-29T15:06:22.281Z","creation":"2025-04-04T02:47:47.066Z"},"accession":"S-EPMC11821908","cross_references":{"pubmed":["39939579"],"doi":["10.1038/s41467-025-56657-5"]}}