Extracellular trap can be trained as a memory response

Abstract

Extracellular trap (ET) appears as a double-edged sword for the host since it participates in host immune defense by entrapping pathogens, while excessive ET release also contributes to various diseases progression including atherosclerosis, cancer, and autoimmune disorders. A better understanding of ET formation and regulation will be beneficial for developing strategies for infection control and ET-associated disease treatment. There is some evidence indicating that prior infection can enhance extracellular killing. Neutrophils from cancer or sepsis are predisposed to generate ET. It is reasonable to suspect that ET may be trained to form as a memory response, just like cytokine memory response termed "trained immunity." The mice were intraperitoneally injected with heat-killed <i>Candida albicans</i> (HK-<i>C. albicans</i>), 3 days later bone marrow-derived macrophages (BMDM) were isolated and challenged with <i>Clostridium perfringens</i> as a second stimulation. We found that HK-<i>C. albicans</i> priming enhanced ET formation upon <i>Clostridium perfringens</i> infection, accompanied by increased extracellular killing capacity. Mannan priming also enhanced ET formation. Since ETs memory was induced in chicken PBMC, ETs memory may be evolutionarily conserved. Moreover, mTOR was required for ETs memory response. Collectively, this study showed that ETs can be trained as a memory response and indicated that memory property of ETs should be considered during the understanding of recurrent infection and ET-associated disorders.