β-Glucan Protects Against Sepsis-Induced Kupffer Cell Loss by Inhibiting Pyroptosis and Promoting Self-Renewal

Area of Science:

• Immunology
• Microbiology
• Hepatology

Background:

• Sepsis involves a dysregulated host response leading to organ failure.
• Kupffer cells (KCs) are crucial for liver immunity during sepsis but are depleted.
• KC depletion increases bacterial load and mortality in sepsis.

Purpose of the Study:

• To investigate the protective effects of beta-glucan on sepsis-induced KC loss.
• To elucidate the mechanisms underlying beta-glucan's action in sepsis.
• To explore beta-glucan's potential as an immunomodulatory therapy for sepsis.

Main Methods:

• Administered beta-glucan to a sepsis model.
• Assessed KC survival and proliferation.
• Analyzed inflammatory pathways, including NLRP3 and GSDMD-mediated pyroptosis.
• Investigated the role of c-Maf and MafB in KC self-renewal.

Main Results:

• Beta-glucan treatment significantly reduced KC depletion during sepsis.
• Beta-glucan attenuated KC death by suppressing NLRP3 and GSDMD-mediated pyroptosis.
• Beta-glucan promoted KC self-renewal by downregulating c-Maf and MafB.
• Circulating bacterial load was reduced following beta-glucan treatment.

Conclusions:

• Beta-glucan protects against sepsis-induced Kupffer cell loss.
• Beta-glucan enhances hepatic macrophage regeneration through novel mechanisms.
• Beta-glucan represents a promising therapeutic strategy to bolster immune defense in sepsis.