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This study investigated how\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    \u03b2-glucan (BG)-induced macrophage training reshapes subsequent inflammatory and antimicrobial responses to EPS. Peritoneal macrophages from C57BL\/6 mice were trained\n                    <jats:italic>in vitro<\/jats:italic>\n                    with BG and subsequently stimulated with EPS purified from a clinical\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    isolate obtained from a patient with severe cystic fibrosis. Cytokines, prostaglandin E\n                    <jats:sub>2<\/jats:sub>\n                    (PGE\n                    <jats:sub>2<\/jats:sub>\n                    ), and nitric oxide (NO) were quantified, and global proteomic profiling was performed. BG training amplified EPS-induced secretion of TNF-\u03b1, IL-6, and additional pro-inflammatory mediators. Trained macrophages also showed markedly increased PGE\n                    <jats:sub>2<\/jats:sub>\n                    production, minimal NO release, and reduced phagocytic activity. Proteomic analyzes confirmed upregulation of PGE\n                    <jats:sub>2<\/jats:sub>\n                    -biosynthetic enzymes and suppression of inducible NO synthase, along with enhanced expression of antimicrobial and immunoregulatory factors, including platelet factor 4, antileucoproteinase, C1q components, and selected chemokines. These data reveal a previously uncharacterized macrophage state\u2014neither M1 nor M2\u2014emerging specifically from BG training and defined by high PGE\n                    <jats:sub>2<\/jats:sub>\n                    and low NO production in response to EPS.\n                    <jats:italic>S. cerevisiae<\/jats:italic>\n                    BG training reprograms EPS-stimulated macrophages toward a distinct, non-classical trained-immunity phenotype characterized by elevated PGE\n                    <jats:sub>2<\/jats:sub>\n                    and suppressed NO production. This newly defined phenotype represents a novel form of trained immunity and highlights the dual proinflammatory and immunoregulatory roles of macrophage-derived PGE\n                    <jats:sub>2<\/jats:sub>\n                    . These findings suggest that targeted macrophage reprogramming may offer a promising therapeutic strategy for mitigating\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    biofilm-driven chronic inflammation, including in cystic fibrosis.\n                  <\/jats:p>","DOI":"10.2478\/aite-2026-0014","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T09:04:23Z","timestamp":1780304663000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Saccharomyces cerevisiae<\/i>\n                    \u03b2-Glucan Training Induces a Nonclassical PGE\n                    <sub>2<\/sub>\n                    \u2212\n                    <sup>High<\/sup>\n                    \/NO\u2212\n                    <sup>Low<\/sup>\n                    Macrophage Phenotype in Response to\n                    <i>Pseudomonas aeruginosa<\/i>\n                    Exopolysaccharide"],"prefix":"10.2478","volume":"74","author":[{"given":"Marta","family":"Ciszek-Lenda","sequence":"first","affiliation":[{"name":"Department of Immunology, Faculty of Medicine , Jagiellonian University Medical College , Krakow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Majka","sequence":"additional","affiliation":[{"name":"Department of Immunology, Faculty of Medicine , Jagiellonian University Medical College , Krakow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Suski","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine , Jagiellonian University Medical College , Krakow , Poland"},{"name":"Proteomics Laboratory , Center for the Development of Therapies for Civilization and Age-Related Diseases , Jagiellonian University Medical College , Krakow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"G\u00f3rska","sequence":"additional","affiliation":[{"name":"Department of Microbiology , Laboratory of Microbiome Immunobiology, Hirszfeld Institute of Immunology and Experimental Therapy , Polish Academy of Sciences , Wroclaw , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edyta","family":"Goli\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Public Health, Faculty of Veterinary Medicine , University of Agriculture in Cracow , Krakow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela","family":"Siemi\u0144ska","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine , University of Agriculture , Krakow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafa\u0142","family":"Olszanecki","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine , Jagiellonian University Medical College , Krakow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Strus","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Public Health, Faculty of Veterinary Medicine , University of Agriculture in Cracow , Krakow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janusz","family":"Marcinkiewicz","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine , University of Agriculture , Krakow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,5,31]]},"reference":[{"key":"2026072522431367879_j_aite-2026-0014_ref_001","doi-asserted-by":"crossref","unstructured":"Allione A, Bernabei P, Bosticardo M et al. 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