Editorial: Neutrophil extracellular traps: mechanistic and functional insight

NET markers were previously detected in the plasma of traumatic brain injury (TBI) patients. Coagulopathy contributes to the majority of deaths and disabilities associated with TBI (10). Previous evidence supports the critical role of NETs contributing to an abnormal coagulation state in the acute phase of TBI. New insights into the role of NET formation in TBI and its impact on neuronal pyroptosis was provided by Yiyao Cao et al. The authors showed that inhibiting NET formation can prevent NLRP1-dependent neuronal pyroptosis in mice with TBI. The study also highlights the involvement of the STING/IRE1α pathway in this process. These findings suggest that targeting NET formation and the STING/IRE1α pathway may present a novel treatment regimen for mitigating brain damage following TBI (11).The generation of ROS by activated neutrophils is one of their fundamental functions. This process can be both positive, facilitating the fight against infection, and negative, leading to tissue damage, e.g. in autoimmune diseases. Neutrophils are known to generate ROS via either NADPH oxidase or mitochondria. In a brief research report Azzouz D. & Nades P. discussed the process of NETosis, specifically in response to ultraviolet (UV) radiation, highlighting the role of mitochondria in generating ROS. Furthermore, the authors show that DNA repair machinery, acting in response to DNA oxidation, leads to the formation of DNA nicks. The accumulation of these DNA nicks results in the opening of chromatin and the release of NETs. The study provides insights into the molecular mechanisms underlying UV-induced NETosis and suggests that base excision repair steps are involved in this process. Further exploring of these mechanisms can contribute to a better understanding of the immune response to UV damage and potentially lead to the development of a new therapeutic approach (12).The role of mitochondria is not restricted to simply being the source of ROS required for NET formation. Notably, mitochondria can also provide DNA for the NET scaffold (13). This aspect of NET formation was studied by Gigon L. & Fettrelet T. Authors focused on the role of two proteins, Syntaxin-4 and SNAP23, in neutrophil's biology, including degranulation, ROS production and the release of mitochondrial DNA (mtDNA) during NET formation. The study reveals that these proteins are involved in degranulation and synthesis of ROS, but they do not play a role in the release of mtDNA during NET formation. This finding shed a new light into various mechanisms and molecules governing neutrophils' strategies to fight infections of NET formation (14).The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are a group of rare autoimmune disorders characterized by the presence of serum antibodies (ANCAs) directed against neutrophil proteases -proteinase 3 (PR3) or myeloperoxidase (MPO). ANCA-mediated neutrophil activation leads to ROS production, cytokine release, NET formation and subsequent vascular damage (15). Shiratori-Aso S. & Nakazawa D. explored the involvement of NETs in ANCAassociated vasculitis. The authors discuss how NETs are released in response to ANCA antibodies, contributing to the pathogenesis of the disease. They also implicate the potential role of NETs in promoting tissue damage and autoimmunity in ANCA-associated vasculitis, indicating that targeting NETs could be a potential treatment (16).Neutrophils are the most abundant group of white blood cells in adult humans, able to fight infections caused by various pathogens, including bacteria and viruses. However, in protozoan infections such as with Toxoplasma gondii, neutrophils can also contribute to the spread of infection by acting as a reservoir for the multiplication of pathogens. The relationship between human NETs and Toxoplasma gondii infection was discussed by Macedo S.I. et. al. The authors found that NETs formed in response to Toxoplasma gondii did not affect the parasite's ability to infect and replicate within the host cells. This suggests that Toxoplasma gondii has developed mechanisms to evade or withstand the effects of NETs, enabling it to establish infection effectively. This study sheds light on the intricate host-parasite interactions and provides evidence leading to deeper understanding of the immune responses against Toxoplasma gondii infection (17).NETs and their components can be detected not only in infected or inflamed tissues, but also in various biological fluids, including blood, bronchoalveolar lavage fluid (BALF) (18), and cerebrospinal fluid (CSF) (19). Zawrotniak M et al. explored the presence and role of NETs in the upper respiratory tract secretions of individuals with infectious and allergic rhinitis. The study shows that NETs were present in nasal secretions of individuals with both infectious and allergic rhinitis. Furthermore, the composition and properties of the NETs differed between these two respiratory disorders, suggesting that NETs may contribute differently to the pathogenesis of these conditions. Understanding the role of NETs in rhinitis could provide valuable insights for developing targeted therapies for these respiratory diseases (20).Overall, the articles compiled in this 'Research Topic' offer a comprehensive understanding of the vital role of NET formation. They delve into the mechanisms of NET formation, shedding light on the involvement of specific proteins and mitochondria. These studies also provide valuable insights into the intricate interactions between NETs and infections. By further exploring the mechanism of NET formation and their implications in clinical settings, we can pave the way for novel therapeutic approaches.