B-1a cells scavenge NETs to attenuate sepsis

Area of Science:

• Immunology
• Sepsis Pathophysiology
• Cellular Biology

Background:

• Neutrophil extracellular traps (NETs) are crucial for pathogen defense but contribute to sepsis-induced inflammation and tissue damage when overproduced.
• Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern that promotes NET formation during sepsis.
• B-1a cells are regulatory B lymphocytes producing natural IgM and IL-10, with a potential role in mitigating sepsis.

Purpose of the Study:

• To investigate the role of B-1a cells in clearing NETs and preventing sepsis-induced injury.
• To elucidate the mechanism by which B-1a cells regulate NET formation and phagocytosis.

Main Methods:

• Sepsis was induced in mice using intraperitoneal injection of Escherichia coli.
• Peritoneal B-1a cell counts were assessed via flow cytometry.
• B-1a cells were replenished intraperitoneally in septic mice; NET formation was analyzed in neutrophils co-cultured with B-1a cells (contact vs. non-contact) and stimulated with eCIRP.

Main Results:

• Septic mice showed a significant decrease in peritoneal B-1a cells.
• B-1a cell replenishment reduced NETs, inflammation, and injury markers, and increased survival in septic mice.
• B-1a cells inhibited eCIRP-induced NET formation in a contact-dependent manner and promoted NET phagocytosis via natural IgM.

Conclusions:

• B-1a cells play a protective role in sepsis by reducing NET burden.
• Direct cell-to-cell contact and natural IgM-mediated phagocytosis are key mechanisms for B-1a cell-mediated NET clearance.
• B-1a cells internalize and lyse NETs, mitigating sepsis-induced pathology.