Neutrophils are the most abundant circulating innate immune cells and comprise the first immune defense line, as they are the most rapidly recruited cells at sites of infection or inflammation. Their main microbicidal mechanisms are degranulation, phagocytosis, cytokine secretion and the formation of extracellular traps. Neutrophil extracellular traps (NETs) are a microbicidal mechanism that involves neutrophil death. Since their discovery, in vitro and in vivo neutrophils have been challenged with a range of stimuli capable of inducing or inhibiting NET formation, with the objective to understand its function and regulation in health and disease. These networks composed of DNA and granular components are capable of immobilizing and killing pathogens. They comprise enzymes such as myeloperoxidase, elastase, cathepsin G, acid hydrolases and cationic peptides, all with antimicrobial and antifungal activity. Therefore, the excessive formation of NETs can also lead to tissue damage and promote local and systemic inflammation. Based on this concept, in this review, we focus on the role of NETs in different infectious and inflammatory diseases of the mucosal epithelia and skin.

Neutrophil extracellular traps (NETs) require reactive oxygen species (ROS) to eliminate pathogens by inducing oxidative stress. However, this process can also cause tissue damage to the host. Neutrophils contain high concentrations of vitamin C (1.5 mM) compared to the bloodstream (0.1 mM), and this antioxidant can interact with vitamin E and glutathione (GSH) inside the cell to maintain the redox balance. Previous studies have investigated the effect of vitamins E or C and N-acetyl cysteine (NAC) on NET formation, but the interactions of these molecules in neutrophils remain unknown. In this study, we investigated the effect of antioxidants alone and two combinations on NET formation and oxidative stress. Neutrophils were pre-loaded with GSH + NAC or vitamin E + vitamin C + GSH + NAC (termed ALL), and LPS-induced NET formation was assessed using fluorometry and immunofluorescence. Antioxidant effects were evaluated by measuring the total antioxidant capacity (TAC), GSH/GSSG ratio, ROS production, nitrite + nitrate levels, and lipid peroxidation. Our results showed that even low doses of antioxidants are capable of decreasing NETs. Furthermore, the combinations augmented TAC and GSH/GSSG ratio and decreased ROS, nitrites + nitrates, and malondialdehyde (MDA) levels in supplemented neutrophils in vitro.

Ulcerative colitis is a chronic inflammatory bowel disease characterized by persistent inflammation, immune dysregulation, gut microbiota alterations, and impaired epithelial barrier function. Lupinus albus is a legume rich in galactooligosaccharides (GOS) that functions as a prebiotic capable of modulating the gut microbiota and mitigating ulcerative colitis-related damage. This study aimed to elucidate the effect of GOS on gut microbiota modulation and the molecular mechanisms involved in epithelial restoration and inflammation reduction. Fifteen C57BL/6 mice were randomly assigned to three groups (n = 5 per group): control (CTL), ulcerative colitis (UC), and ulcerative colitis + GOS (UC + GOS). UC was induced by administering 2% dextran sulfate sodium (DSS) in drinking water for seven days. The UC + GOS group received 2.5 g/kg BW of GOS via gavage for 14 days. GOS administration improved mucus layer thickness, regulated the expression of tight junction proteins, reduced pro-inflammatory cytokine levels, and modulated the gut microbiota, preventing the loss of richness and diversity. Additionally, the expression of monocarboxylate transporters (MCTs) MCT1 and MCT4 was evaluated, and significant differences were observed between the groups across colon and cecum tissues. These findings suggest that GOS supplementation may play a potential role in attenuating ulcerative colitis by regulating the gut microbiota and the metabolic state of intestinal cells.

This study aimed to summarize the epidemiological and clinical characteristics of COVID-19 from Western Mexico people during 2020. A retrospective analysis from an electronic database of people visiting a sentinel center for molecular SARS-CoV-2 confirmatory diagnosis by RT-PCR from April to December 2020 was carried out for epidemiological and clinical description of COVID-19. Out of 23,211 patients evaluated, 6918 (29.8%) were confirmed for SARS-CoV-2 infection (mean age 38.5 ± 13.99), mostly females (53.8%). Comorbidities, such as diabetes (34.7%), obesity (31.15%), and hypertension (31.8%), presented an increased odds OR = 1.27, CI = 1.14–1.41; OR = 1.08, CI = 1.01–1.16; and OR = 1.09, CI = 0.99–1.19, respectively, for viral-infection. Moreover, fever, headache, and dry cough were the most frequent symptoms. No infection difference among sex was found. Those patients >60 years old were prone to COVID-19 severity (OR = 3.59, CI = 2.10–6.14), evaluated by the number of manifested symptoms, increasing with age. In conclusion, a high SARS-CoV-2 prevalence was found in Western Mexico. Comorbidities were frequent in infected people; nevertheless, no association with disease outcomes was observed, in contrast with the highest disease severity risk found in older patients; however, continuous monitoring should be carried since comorbidities have been reported as aggravating factors. This study can help the health officials for the elaboration of planning efforts of the disease management and others in the future.

Neutrophils are essential for antimicrobial defense through reactive oxygen species (ROS) production, tumor necrosis factor-alpha (TNF-α) release, and neutrophil extracellular trap formation. Lipoic acid, a redox-active antioxidant, modulates activation in human neutrophils. Neutrophils isolated from healthy donors were pretreated with lipoic acid and then exposed to lipopolysaccharide (LPS) or whole Escherichia coli, according to the specific assay. ROS production, NET formation, TNF-α release, bacterial killing, metabolic activity, and cell death were assessed using fluorometric assays, enzyme-linked immunosorbent assay, colony-forming unit assays, MTT reduction, and Annexin V-FITC/propidium iodide flow cytometry. Lipoic acid significantly reduced ROS production and NET formation induced by LPS and Escherichia coli. at 0.5 mM, lipoic acid also reduced E. coli-induced NET formation by approximately 50% and attenuated TNF-α release at early stimulation times. In colony-forming unit assays, lipoic acid did not significantly reduce neutrophil-mediated killing of Escherichia coli or Staphylococcus aureus. Although only neutrophil preparations with high baseline viability were used, Escherichia coli challenge markedly reduced cell viability during the assay; under this condition, lipoic acid pretreatment limited bacteria-induced necrosis and preserved a higher proportion of viable neutrophils. These findings indicate that lipoic acid dampens excessive oxidative and inflammatory neutrophil responses while maintaining measurable bactericidal capacity in vitro.