Neutrophils or polymorphonuclear leukocytes (PMN) are key participants in the innate immune response for their ability to execute different effector functions. These cells express a vast array of membrane receptors that allow them to recognize and eliminate infectious agents effectively and respond appropriately to microenvironmental stimuli that regulate neutrophil functions, such as activation, migration, generation of reactive oxygen species, formation of neutrophil extracellular traps, and mediator secretion, among others. Currently, it has been realized that activated neutrophils can accomplish their effector functions and simultaneously activate mechanisms of cell death in response to different intracellular or extracellular factors. Although several studies have revealed similarities between the mechanisms of cell death of neutrophils and other cell types, neutrophils have distinctive properties, such as a high production of reactive oxygen species (ROS) and nitrogen species (RNS), that are important for their effector function in infections and pathologies such as cancer, autoimmune diseases, and immunodeficiencies, influencing their cell death mechanisms. The present work offers a synthesis of the conditions and molecules implicated in the regulation and activation of the processes of neutrophil death: apoptosis, autophagy, pyroptosis, necroptosis, NETosis, and necrosis. This information allows to understand the duality encountered by PMNs upon activation. The effector functions are carried out to eliminate invading pathogens, but in several instances, these functions involve activation of signaling cascades that culminate in the death of the neutrophil. This process guarantees the correct elimination of pathogenic agents, damaged or senescent cells, and the timely resolution of the inflammation that is essential for the maintenance of homeostasis in the organism. In addition, they alert the organism when the immunological system is being deregulated, promoting the activation of other cells of the immune system, such as B and T lymphocytes, which produce cytokines that potentiate the microbicide functions.

The purpose of this paper is to review current information about the role of inflammation caused by Helicobacter pylori (H. pylori) infection in neurological diseases such as Parkinson's disease, Alzheimer's disease, Guillain-Barré syndrome, multiple sclerosis, and other inflammatory diseases including ischemic stroke. Infection with H. pylori usually persists throughout life, resulting in a chronic inflammatory response with local secretion of numerous inflammatory mediators including chemokines [interleukin (IL)-8, macrophage chemotactic protein (MCP)-1, growth-regulated oncogene (GRO)-α] and cytokines [IL-1β, tumor necrosis factor (TNF)-α, IL-6, IL-12, interferon (IFN)-γ], which can pass into the circulation and have a systemic effect. The persistence of detectable systemic and local concentrations of inflammatory mediators is likely to alter the outcome of neurological diseases. These proinflammatory factors can induce brain inflammation and the death of neurons and could eventually be associated to Parkinson's disease and also may be involved in the development of Alzheimer's disease. However, most neurological diseases are the result of a combination of multiple factors, but the systemic inflammatory response is a common component and determinant in the onset, evolution, and outcome of diseases. However, more studies are needed to allow understanding of the effects and mechanisms by which the inflammatory response generated by H. pylori infection affects neurological diseases.

Gastric adenocarcinoma is the third most common cause of cancer-associated death worldwide. Helicobacter pylori infection activates a signaling cascade that induces production of cytokines and chemokines involved in the chronic inflammatory response that drives carcinogenesis. We evaluated circulating cytokines and chemokines as potential diagnostic biomarkers for gastric cancer. We included 201 healthy controls and 162 patients with distal gastric cancer who underwent primary surgical resection between 2009 and 2012 in Mexico City. The clinical and pathological data of patients were recorded by questionnaire, and the cancer subtype was classified as intestinal or diffuse. Pathological staging of cancer was based on the tumor–node–metastasis staging system of the International Union Against Cancer. Concentrations of IL-1β, IL-6, TNF-α, IL-10, and MCP-1 in serum were measured using multiplex analyte profiling technology and concentrations of IL-8, IFN-γ, and TGF-β in plasma were measured using enzyme-linked immunosorbent assay. Levels of IL-1β, IL-6, IFN-γ, and IL-10 were significantly higher and that of MCP-1 was lower in gastric cancer patients compared with controls. No differences in IL-8 or TNF-α levels were observed between gastric cancer and controls. IFN-γ and IL-10 were significantly higher in both intestinal and diffuse gastric cancer, whereas IL-1β and IL-6 were higher and TGF-β lower only in intestinal gastric cancer; MCP-1 was lower only in diffuse gastric cancer. IFN-γ and IL-10 levels were significantly higher in early (I/II) and late stage (III/IV) gastric cancer; IL-1β and IL-8 were higher and MCP-1 was lower only in late stage (IV) patients. Receiver-operating characteristic analysis showed that for diagnosis of GC, IL-6 had high specificity (0.97) and low sensitivity (0.39), IL-10 had moderate specificity (0.82) and low sensitivity (0.48), and IL-1β and IFN-γ showed low specificity (0.43 and 0.53, respectively) and moderate sensitivity (0.76 and 0.71, respectively). Increased levels of IL-6, IFN-γ, and IL-10 might be useful as diagnostic biomarkers for GC; however, this needs to be confirmed with larger number of patients and with control groups other than blood donors, properly age paired. IL-1β, IL-6, MCP-1, and TGF-β differentiate intestinal from diffuse GC. IFN-γ and IL-10 might be useful for diagnosis of early stage GC, and IL-1β, IL-8, and MCP-1 for late stages of the disease.

TLRs and NLRs participate in the immune system recognition of Helicobacter pylori. However, little is known about the mechanisms leading to inflammasome activation by H. pylori and if NLRs in neutrophils are involved in the process. We studied how NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome components are involved in IL-1β maturation in human neutrophils in response to the infection and if they are dependent on T4SS (type IV secretion system) and TLRs. Human neutrophils were cultured and infected with the 26695 or the VirD4⁻ H. pylori strains; the IL-1β concentration was analyzed by ELISA, and we also evaluated the activation of TLRs 2 and 4. The infection of neutrophils with both strains of H. pylori induced production of IL-1β and expression of the NLRP3 inflammasome components such as apoptosis-associated speck-like protein with CARD domain and NLRP3 protein. The infection also increased the activity of caspase-1, which is required for the maturation of IL-1β. Our study shows, for the first time, that H. pylori infection induces the expression and activation of components of NLRP3 inflammasomes in human neutrophils and that the activation is independent of a functional T4SS and TLR2 and TLR4.

The innate immune response to Helicobacter pylori infection is beginning to be understood and recent works support a role for Toll-like receptors (TLR

Helicobacter pylori infection is recognized as the main risk factor for gastric cancer (GC), the fifth most common neoplasia worldwide. H. pylori interacts with the immune system, disrupting the cytokine network and inducing chronic inflammation. This work aimed to evaluate the association between single nucleotide polymorphisms (SNPs) in selected cytokine gene promoters and GC. The study included 359 subjects, 125 GC patients, 109 intestinal metaplasia (IM) patients and 125 asymptomatic controls. DNA was extracted from white blood cells and nine SNPs in cytokine gene promoters were genotyped using predesigned 5′-endonulease assays. The association of the SNPs with IM and GC was evaluated using multinomial regression models. Both genotypes, TC (OR = 0.51, 95% CI = 0.27–0.98) and TT (OR = 0.42, 95% CI = 0.20–0.91) in the locus − 509 of the TGF-β promoter were significantly associated with GC. The TT genotype in the locus − 819 of the IL-10 promoter was also significantly associated with GC (OR = 0.37, 95% CI = 0.17–0.81). No significant association was found with SNPs IL-4 –590 T/C (rs1800629), IL-6 –573G/C (rs1800796), IL-10 –592C/A (rs1800872), IL-10 –1082A/G (rs1800896), and, IFN-γ –1615C/T (rs2069705). SNPs in TGFβ (− 509 C/T, rs1800469) and IL-10 (− 819 C/T, rs1800871) promoters were associated with a lower risk for GC in a Mexican population.