Intraperitoneal extracellular trap-derived proteins mediate the amplification of vaccine-induced immune responses in...

Myeloid cells are capable of releasing web-like extracellular structures composed of DNA and granular proteins, known as extracellular traps (ETs), which function to eliminate invading pathogens and modulate immune responses. Intraperitoneal vaccine administration has been demonstrated to induce ETs, but their roles in vaccine-mediated immune responses remain largely unknown. In this study, we show that a protein subunit vaccine triggers the release of ETs in the peritoneal cavity of teleost fish. Pharmacological inhibition of ET formation by 4-aminobenzoic acid hydrazide (ABAH) or enzymatic degradation of ETs by DNase I significantly reduces CD4-1⁺ and CD4-2⁺ T cell proportions in immune organs, decreases IgM⁺ B cell frequency in peripheral blood, and lowers antigen-specific antibody titers. Proteomic profiling of ETs generated in vivo and in vitro reveals that ET-derived proteins are enriched in molecules involved in immune regulatory pathways associated with macrophage activation, antigen presentation, and T cell proliferation and differentiation. Collectively, our findings indicate that ET-derived proteins act as core molecular scaffolds to boost vaccine-induced adaptive immune responses, offering novel insight into the bridging mechanisms between innate and adaptive immunity.