Masking of typical TLR4 and TLR5 ligands modulates inflammation and resolution by Helicobacter pylori.

Helicobacter pylori is a paradigm of chronic bacterial infection and is associated with peptic ulceration and malignancies. H. pylori uses specific masking mechanisms to avoid canonical ligands from activating Toll-like receptors (TLRs), such as lipopolysaccharide (LPS) modification and specific flagellin sequences that are not detected by TLR4 and TLR5, respectively.

Toll-like Receptor 5 Activation by the CagY Repeat Domains of Helicobacter pylori.

Helicobacter pylori (Hp) is an important human pathogen associated with gastric inflammation and neoplasia. It is commonly believed that this bacterium avoids major immune recognition by Toll-like receptors (TLRs) because of low intrinsic activity of its flagellin and lipopolysaccharides (LPS). In particular, TLR5 specifically detects flagellins in various bacterial pathogens, while Hp evolved mutations in flagellin to evade detection through TLR5.

Avoids the Critical Activation of NLRP3 Inflammasome-Mediated Production of Oncogenic Mature IL-1β in Human Immune Cells.

persistently colonizes the human stomach, and is associated with inflammation-induced gastric cancer. Bacterial crosstalk with the host immune system produces various inflammatory mediators and subsequent reactions in the host, but not bacterial clearance. Interleukin-1β (IL-1β) is implicated in gastric cancer development and certain gene polymorphisms play a role in this scenario.

T4SS-dependent TLR5 activation by Helicobacter pylori infection.

Toll-like receptor TLR5 recognizes a conserved domain, termed D1, that is present in flagellins of several pathogenic bacteria but not in Helicobacter pylori. Highly virulent H. pylori strains possess a type IV secretion system (T4SS) for delivery of virulence factors into gastric epithelial cells.

Tailor-Made Detection of Individual Phosphorylated and Non-Phosphorylated EPIYA-Motifs of Oncoprotein CagA.

The gastric pathogen and carcinogen encodes a type IV secretion system for translocation of the effector protein CagA into host cells. Injected CagA becomes tyrosine-phosphorylated at the five amino acid residue Glutamate-Proline- Isoleucine-Tyrosine-Alanine (EPIYA)-sequence motifs. These phosphorylated EPIYA-sites represent recognition motifs for binding of multiple host factors, which then manipulate signaling pathways to trigger gastric disease.

Mechanisms of Inflammasome Signaling, microRNA Induction and Resolution of Inflammation by Helicobacter pylori.

Inflammasome-controlled transcription and subsequent cleavage-mediated activation of mature IL-1β and IL-18 cytokines exemplify a crucial innate immune mechanism to combat intruding pathogens. Helicobacter pylori represents a predominant persistent infection in humans, affecting approximately half of the population worldwide, and is associated with the development of chronic gastritis, peptic ulcer disease, and gastric cancer. Studies in knockout mice have demonstrated that the pro-inflammatory cytokine IL-1β plays a central role in gastric tumorigenesis.

Immune Cell Signaling by Helicobacter pylori: Impact on Gastric Pathology.

Helicobacter pylori represents a highly successful colonizer of the human stomach. Infections with this Gram-negative bacterium can persist lifelong, and although in the majority of cases colonization is asymptomatic, it can trigger pathologies ranging from chronic gastritis and peptic ulceration to gastric cancer. The interaction of the bacteria with the human host modulates immune responses in different ways to enable bacterial survival and persistence.

Helicobacter pylori controls NLRP3 expression by regulating hsa-miR-223-3p and IL-10 in cultured and primary human immune cells.

Inflammasome-mediated production of mature IL-1β and IL-18 cytokines represents an important innate immune response against infecting pathogens. Helicobacter pylori, one of the most successful and persistent human pathogens, induces severe inflammation leading to gastritis and more serious gastric diseases. H.

Inflammasome Activation by Helicobacter pylori and Its Implications for Persistence and Immunity.

Infection with the Gram-negative pathogen Helicobacter pylori is the most prevalent chronic bacterial infection affecting about 50 % of the human world population and is the main risk factor for gastric cancer development. The pro-inflammatory cytokine IL-1β plays a crucial role in the development of gastric tumors, and polymorphisms in the IL-1 gene cluster resulting in increased IL-1β production have been associated with increased risk for gastric cancer. Recently, Helicobacter pylori was postulated to activate the inflammasome in human and mouse immune cells, and the molecular mechanisms and the bacterial virulence factors activating the inflammasome were elucidated in cell culture as well as animal models.

Interplay of the Gastric Pathogen Helicobacter pylori with Toll-Like Receptors.

Toll-like receptors (TLRs) are crucial for pathogen recognition and downstream signaling to induce effective immunity. The gastric pathogen Helicobacter pylori is a paradigm of persistent bacterial infections and chronic inflammation in humans. The chronicity of inflammation during H.

Signal transduction of Helicobacter pylori during interaction with host cell protein receptors of epithelial and immune cells.

Helicobacter pylori infections can induce pathologies ranging from chronic gastritis, peptic ulceration to gastric cancer. Bacterial isolates harbor numerous well-known adhesins, vacuolating cytotoxin VacA, protease HtrA, urease, peptidoglycan, and type IV secretion systems (T4SS). It appears that H.

Induction of TLR-2 and TLR-5 expression by Helicobacter pylori switches cagPAI-dependent signalling leading to the secretion of IL-8 and TNF-α.

Helicobacter pylori is the causative agent for developing gastritis, gastric ulcer, and even gastric cancer. Virulent strains carry the cag pathogenicity island (cagPAI) encoding a type-IV secretion system (T4SS) for injecting the CagA protein. However, mechanisms of sensing this pathogen through Toll-like receptors (TLRs) and downstream signalling pathways in the development of different pathologies are widely unclear.

Blood zinc protoporphyrin, serum total protein, and total cholesterol levels in automobile workshop workers in relation to lead toxicity: Our experience.

Blood zinc protoporphyrin (ZPP), serum total protein (TP), and total cholesterol (TC) levels in automobile workshop workers in relation to lead toxicity were analysed. In the present study, automobile workshop workers (healthy male workers at an age between 28 and 35 from four major automobile workshops in Kottayam, Kerala State, India) and the control (male healthy adults at an age between 28 and 35 residing at Aymanam, a distant village at Kottayam District, Kerala having reduced or no chance of lead exposure) displayed significant difference in blood lead (BPb) and blood ZZP (BZPP) level. The mean value of BPb in automobile workshop workers was 15.