In this study, we conducted a retrospective analysis of the clinical data of patients with central nervous system infectious diseases, mainly including MPO, blood white cell count, cerebrospinal fluid white cell count, cerebrospinal fluid protein, and other clinical diagnostic indicators. We focused on the clinical value of MPO as a diagnostic indicator for Suppurative meningitis. The results of this study show that MPO can serve as a clinical marker for the Severity assessment of Suppurative meningitis.
Neutrophil Extracellular Traps (NETs) refer to helical structures primarily composed of DNA, mainly formed by neutrophils[13]. NETs enhance the body's immune defense against pathogens by releasing intracellular molecules and enzymes to trap and restrict the spread of pathogens[14]. However, in situations where a large number of pathogens exist, the release of NETs may become excessive, thereby leading to adverse consequences such as tissue damage, seriously affecting the health of the patient[15].
Neutrophils play a crucial role in infectious diseases. The various biological functions of these cells make them an important weapon in protecting the body from infection[16].
The mechanism by which neutrophils kill bacteria by releasing NETs was discovered by the Brinkmann team in 2004. NETs are a net-like structure released to the outside of neutrophils after they are activated, with a skeleton composed of cell-free deoxyribonucleic acid (cfDNA) and embedded with proteins such as histones, neutrophil elastase, myeloperoxidase (MPO), and tissue proteinase G[7]. The formation of NETs originates from a type of neutrophil death called NETosis, which is neither apoptosis nor necrosis in the usual sense. It is generally believed that there are three modes of NETosis:
(1) "Suicidal" NETosis: In the final stage of the neutrophil cycle, the nuclear membrane and cytoplasmic granule membrane dissolve, allowing chromatin in the nucleus and granules in the cytoplasm to fully contact each other. As the cell membrane ruptures, these components are discharged outside the cell, ultimately forming a net-like structure with DNA as its skeleton and various proteins embedded on it.[17] This pattern depends on the reduced form of coenzyme II oxidase to activate reactive oxygen, promoting nuclear membrane dissolution and hence NETs formation, after which the neutrophil dies[18].
(2) "Vital" NETosis: Cells recognize Toll-like receptors and complement receptor C3, activating extracellular regulated protein kinases (ERK), phosphatidylinositol 3 kinase (PI3K), and tyrosine protein kinase, causing nuclear DNA to be released via mechanisms like cell vomiting[19].
(3) Mitochondrial DNA NETosis: The cell, upon recognizing complement C5a and lipopolysaccharides, substitutes mitochondrial DNA for nuclear DNA in the formation of NETs[20].
Under normal circumstances, due to the existence of the blood-brain barrier, neutrophils are blocked outside the cerebrospinal fluid, with monocytes typically dominant in the cerebrospinal fluid. However, under various pathological conditions, such as infection, trauma, cerebral ischemia, neurodegenerative infiltration, or autoimmunity, neutrophils will enter the cerebrospinal fluid and release NETs[14]. Whether and how the differences in NET components affect their function still requires further research. However, MPO, as a major component of the antibacterial substances in neutrophils, has extremely high value for indicative detection. This is also the theoretical basis for MPO being able to detect Suppurative meningitis.
Currently, there are no existing research literature on the clinical diagnosis of MPO. This study verifies the clinical diagnostic value of MPO in Suppurative meningitis and attempts to determine its diagnostic reference value, demonstrating a certain degree of innovation. The detection method merely requires ELISA measurement of cerebrospinal fluid, which is convenient for laboratory operations, cost-effective, and suitable for initial detection upon hospital admission, potentially improving the diagnostic efficiency for Suppurative meningitis. However, there are some shortcomings in this experiment. Firstly, since this study is retrospective, it is difficult to control for confounding factors. Secondly, due to the single-center nature of the study with a small sample size, bias risk is inevitably present. Thirdly, this experiment applies functional metagenomic second-generation sequencing, only selecting patients with clear pathogenic diagnostic basis. However, given the complexity of clinical situations, it may overlook some undetected patients. Centre nature of this study, conducted with a small sample size, there inevitably exists a risk of bias. Thirdly, this experiment uses second-generation sequencing of the functional metagenome, only selecting patients with a clear basis for pathogen diagnosis, yet the complexity of clinical situations may lead to overlooking some undetected patients.
After the discovery of neutrophil extracellular traps (NETs) as a new manifestation of neutrophil immune function, the ability of NETs to capture microorganisms has sparked a great deal of research interest. Studies on the mechanisms of NETs have gradually deepened, and researchers have discovered their various effects on blood vessels and diseases. As an emerging field of research, the functional roles of NETs are considered to be a double-edged sword, as their immunoregulatory properties may have unknown beneficial effects in immune defense. Several factors determine whether NETs are beneficial or harmful. Dysregulation of constitutive activation, inhibitory mechanisms, and excessive production of NETs can be prominent pathological mechanisms that contribute to diseases. Therefore, the content of neutrophil extracellular traps has high diagnostic value in Suppurative meningitis. Considering the numerous proteins within NETs, in this study we focused on investigating the diagnostic value of NETs in central nervous system infectious diseases through MPO analysis, thus concluding that MPO has high diagnostic value in the diagnosis of Suppurative meningitis. However, there are still many directions awaiting discovery by future researchers. In the modern era with advancing diagnostic methods, our research on neutrophil extracellular traps aims to better understand the functions and influences of NETs on immunity, ultimately allowing us to inhibit and eliminate harmful functions without interfering with beneficial functions.