{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:06:52Z","timestamp":1789103212227,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Pseudomonas aeruginosa ST235 isolates drive a distinct macrophage inflammatory program characterized by IL-1\u03b2 axis dominance and suppression of canonical NF-\u03baB-associated cytokine responses. In THP-1-derived macrophages, ST235 isolates induce robust inflammasome activation, resulting in elevated IL-1\u03b2 production and altered cell death responses, while eliciting markedly lower TNF\u03b1, IL-6, IL-8, and IL-10 responses than non-ST235 isolates. In contrast, nonST235 isolates preferentially stimulate NF-\u03baB-dependent cytokine production with weaker inflammasome activation. Mechanistically, ST235 infection suppresses NF-\u03baB signaling and reduces caspase-1 expression, whereas caspase-8 remains unchanged, indicating that increased IL-1\u03b2 production can be due to alternative inflammasome pathways or posttranscriptional modifications. Rapid macrophage death further restricts overall cytokine production, reinforcing an IL-1\u03b2-dominant inflammatory profile. ST235 isolates also selectively reprogram M2-polarized macrophages toward an M1 phenotype, as demonstrated by increased CD86 expression, while both isolate groups promote M1 polarization in unpolarized macrophages. Importantly, pyoverdine purified from ST235 isolates reproduced aspects of these responses by inducing IL-1\u03b2 production and cytotoxicity more effectively than pyoverdine from non-ST235 isolates, supporting a potential contribution of ST235-derived pyoverdine to the IL-1\u03b2-dominant inflammatory phenotype. Collectively, these findings suggest that ST235 isolates modulate macrophage immune responses through suppression of NF-\u03baB-associated responses and promotion of IL-1\u03b2-dominant inflammation, providing insights into the virulence of this high-risk clone and highlighting potential therapeutic targets. Significant statement: ST235 isolates of P. aeruginosa uniquely modulate macrophage immune responses by robustly activating inflammasome signaling, inducing IL-1\u03b2 expression while suppressing other cytokines, and driving macrophage polarization toward a pro-inflammatory M1 phenotype. These findings highlight distinct pathogenic strategies of ST235 isolates that may inform targeted therapeutic interventions.<\/jats:p>","DOI":"10.3390\/ijms27188040","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:43:16Z","timestamp":1788972196000},"page":"8040","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammasome Dynamics in the High-Risk Clone ST235 with Altered Pyoverdine Structures"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0817-5315","authenticated-orcid":false,"given":"Zeynep G\u00fcl\u00e7e","family":"Tanyola\u00e7","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/s11274-019-2739-1","article-title":"Metabolomic studies of Pseudomonas aeruginosa","volume":"35","author":"Mielko","year":"2019","journal-title":"World J. 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