Basophil Extracellular Traps in Immunity and Disease

Basophil extracellular traps (BETs) represent a recently recognized extracellular effector mechanism whose biology remains far less defined than that of neutrophil extracellular traps. This review critically examines the terminology, molecular composition, signaling requirements, and disease relevance of BET formation. Current evidence supports a rapid, predominantly non-lytic process in which mitochondrial reactive oxygen species promote the externalization of mitochondrial DNA, particularly after IL-3 priming followed by FcεRI or C5a receptor activation. The resulting networks contain mtDNA associated with basophil granule proteins, including basogranulin in humans and mMCP-8 in mice, although their complete proteomic composition and route of cellular export remain unresolved. Functional studies indicate that BETs can immobilize Escherichia coli and Staphylococcus aureus and contribute to extracellular bacterial killing, while in vivo observations place BET release in helminth-associated inflammation and several inflammatory dermatoses. A small cervical cancer study reported circulating BET-like structures during anticancer treatment, although their basophil origin and molecular composition were not comprehensively confirmed and their biological significance remains unknown. By separating direct basophil evidence from mechanisms inferred from other trap-forming cells, this review defines the current experimental boundaries of the field and highlights priorities for mechanistic and translational investigation.