2025/10/02 by Joseph Adams, J. S. Adams, Tingting Li +11
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Immune cells in cancer #Immune responses and vaccinations #Inflammasome and immune disorders
paper · doi:10.1111/imm.70043
crossref issued 2025/10/02 · crossref published 2025/10/02 · crossref published-online 2025/10/02 · openalex publication_date 2025/10/02 · crossref created 2025/10/03 · openalex created_date 2025/10/10 · crossref deposited 2026/01/08 · crossref published-print 2026/02/01 · crossref indexed 2026/07/30 · openalex updated_date 2026/07/31
Sepsis is a life-threatening condition characterised by a dysregulated host response to infection, resulting in systemic inflammation, immune dysfunction, and multi-organ failure. Kupffer cells (KCs), the largest population of tissue-resident 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 β-glucan treatment effectively protects against sepsis-induced KC loss and reduces circulating bacterial load. Mechanistically, β-glucan attenuates KC death by suppressing NLRP3 and gasdermin D (GSDMD)-mediated pyroptosis triggered by bacterial infections. Notably, we identify a previously unrecognised function of β-glucan in markedly enhancing KC self-renewal during sepsis through downregulation of the transcriptional repressors c-Maf and MafB, which are known to inhibit macrophage proliferation. This discovery reveals a novel mechanism of hepatic macrophage regeneration and supports β-glucan as a promising immunomodulatory therapy to preserve liver immune integrity, enhancing antibacterial defence, and reducing the risk of secondary infections in immunocompromised septic hosts.