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Kupffer cells (KCs), the largest population of tissue\u2010resident macrophages in the body, are essential for pathogen clearance, endotoxin detoxification, and maintaining hepatic immune homeostasis during sepsis. However, sepsis induces substantial KC depletion, contributing to increased bacterial burden and mortality. In this study, we demonstrate that \u03b2\u2010glucan treatment effectively protects against sepsis\u2010induced KC loss and reduces circulating bacterial load. Mechanistically, \u03b2\u2010glucan attenuates KC death by suppressing NLRP3 and gasdermin D (GSDMD)\u2010mediated pyroptosis triggered by bacterial infections. Notably, we identify a previously unrecognised function of \u03b2\u2010glucan in markedly enhancing KC self\u2010renewal during sepsis through downregulation of the transcriptional repressors c\u2010Maf and MafB, which are known to inhibit macrophage proliferation. This discovery reveals a novel mechanism of hepatic macrophage regeneration and supports \u03b2\u2010glucan as a promising immunomodulatory therapy to preserve liver immune integrity, enhancing antibacterial defence, and reducing the risk of secondary infections in immunocompromised septic hosts.<\/jats:p>","DOI":"10.1111\/imm.70043","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:50:28Z","timestamp":1759452628000},"page":"286-298","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["\u03b2\u2010Glucan Protects Against Sepsis\u2010Induced Kupffer Cell Loss by Inhibiting Pyroptosis and Promoting Self\u2010Renewal"],"prefix":"10.1111","volume":"177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6310-5495","authenticated-orcid":false,"given":"Joseph","family":"Adams","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences Quillen College of Medicine, East 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