Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo

 Yipp, BG. et al. Nat Med. 18, 1386-93 (2012)

Speaker: Shun-Yi Chien (錢舜益)                                 Time: 13:10~14:00, Mar. 6, 2013

Commentator: Dr. Yee-Shin Lin (林以行 博士)          Place: Room 601

Abstract

Neutrophils are the most abundant leukocytes in the blood and constitute the first line of host defense against invading pathogens. Neutrophils have a short lifespan and they are continuous released from bone marrow to maintain homeostasis. Neutrophils perform their function by engulfing pathogens and degrading them, and are also degranulated for releasing antimicrobial factors to kill extracellular microorganisms [1]. Moreover, neutrophils release their chromatin structures loaded with antimicrobial molecules called, neutrophil extracellular traps (NETs) that can trap and kill microbes [2]. NETosis was suggested to be lytic cell death, but the authors discovered the rapid NET release without cell lysis in a previous article. They hypothesize that rapid NET release may be carried out by viable PMNs in vivo and want to understand the relationship between conventional PMN-mediated and NET-mediated host defense. The authors used intravital microscopy to visualize neutrophil behavior and NETosis. They found NETs were rapidly released from nucleus during acute Gram-positive bacterial infections. Furthermore, both Tlr2^-/- and C3^-/- mice were incapable of releasing NETs, indicating NET formation is regulated by Tlr2 and C3. They showed that PMNs underwent NETosis can remained viable and maintained specific functions such as crawling and phagocytosis. Mice treated with DNase resulted in a significant increase in bacteria and a decrease of skin CFUs, indicating NETs are essential for limiting S. aureus dissemination. Human PMNs injected into mouse skin released NETs and became anuclear in presence of infection. In conclusion, physiological fate of NETosing PMNs is not immediate cell death and the release of NETs is an important response to infection in vivo.

References

1.      Segal AW. How neutrophils kill microbes. Annu Rev Immunol. 23, 197-223 (2005)

2.      Brinkmann, V., et al. Neutrophil extracellular traps kill bacteria. Science. 303, 1532-5 (2004)