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 Candida albicans (HK-C. albicans), 3 days later bone marrow-derived macrophages (BMDM) were isolated and challenged with Clostridium perfringens as a second stimulation. We found that HK-C. albicans priming enhanced ET formation upon Clostridium perfringens 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.

KEYWORDS:

• Extracellular trap
• trained immunity
• trained memory
• innate immune
• memory response
• antimicrobial

Acknowledgments

We would like to express our gratitude to all the people who made this work possible.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

Ethics approval and consent to participate

All animal studies were conducted according to experimental practices and standards approved by the Animal Welfare and Research Ethics Committee at Jilin University (No. 20,150,601).

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China [No. 31972682].