IL-17RA-Mediated Epithelial Cell Activity Prevents Severe Inflammatory Response to Helicobacter pylori Infection.

Helicobacter pylori is a Gram-negative pathogen that colonizes the stomach, induces inflammation, and drives pathological changes in the stomach tissue, including gastric cancer. As the principal cytokine produced by Th17 cells, IL-17 mediates protective immunity against pathogens by inducing the activation and mobilization of neutrophils. Whereas IL-17A is largely produced by lymphocytes, the IL-17 receptor is expressed in epithelial cells, fibroblasts, and hematopoietic cells.

Fatty acids of lipoproteins CagT and Lpp20.

Bacterial lipoproteins are post-translationally modified by the addition of acyl chains that anchor the protein to bacterial membranes. This modification includes two ester-linked and one amide-linked acyl chain on lipoproteins from Gram-negative bacteria. lipoproteins have important functions in pathogenesis (including delivering the CagA oncoprotein to mammalian cells) and are recognized by host innate and adaptive immune systems.

Remodeling of the gastric environment in -induced atrophic gastritis.

colonization of the human stomach is a strong risk factor for gastric cancer. To investigate -induced gastric molecular alterations, we used a Mongolian gerbil model of gastric carcinogenesis. Histologic evaluation revealed varying levels of atrophic gastritis (a premalignant condition characterized by parietal and chief cell loss) in -infected animals, and transcriptional profiling revealed a loss of markers for these cell types.

IL-17 receptor A functions to help maintain barrier integrity and limit activation of immunopathogenic response to infection.

Activation of Th17 cell responses, including the production of IL-17A and IL-21, contributes to host defense and inflammatory responses by coordinating adaptive and innate immune responses. IL-17A and IL-17F signal through a multimeric receptor, which includes the IL-17 receptor A (IL-17RA) subunit and the IL-17RC subunit. IL-17RA is expressed by many cell types, and data from previous studies suggest that loss of IL-17 receptor is required to limit immunopathology in the model of infection.

Essential role of apolipoprotein N-acyltransferase (Lnt) in stomach colonization.

Bacterial lipoproteins are post-translationally modified with acyl chains, anchoring these proteins to bacterial membranes. In Gram-negative bacteria, three enzymes complete the modifications. Lgt (which adds two acyl chains) and LspA (which removes the signal peptide) are essential.

Increased intestinal permeability and downregulation of absorptive ion transporters , , and contribute to diarrhea during infection.

Background & Aim: infection (CDI) is the leading cause of hospital-acquired diarrhea and pseudomembranous colitis. Two protein toxins, TcdA and TcdB, produced by are the major determinants of disease. However, the pathophysiological causes of diarrhea during CDI are not well understood.

Identification of an Essential LolD-Like Protein in Helicobacter pylori.

The localization of lipoprotein (Lol) system is used by Gram-negative bacteria to export lipoproteins to the outer membrane. Lol proteins and models of how Lol transfers lipoproteins from the inner to the outer membrane have been extensively characterized in the model organism Escherichia coli, but in numerous bacterial species, lipoprotein synthesis and export pathways deviate from the E. coli paradigm.

IL-17 Receptor Signaling through IL-17A or IL-17F Is Sufficient to Maintain Innate Response and Control of Immunopathogenesis.

IL-17R signaling is required for control of extracellular pathogens and is also implicated in development of chronic inflammatory processes. The response to the human pathogen results in Th1 and Th17 cell activation and a chronic inflammatory process that can lead to adverse outcomes, such as gastric cancer. Previously, we identified IL-17RA as a requirement for the recruitment of neutrophils and control of colonization in the gastric mucosa.

Loss of Corpus-Specific Lipids in Helicobacter pylori-Induced Atrophic Gastritis.

Helicobacter pylori colonization of the stomach is a strong risk factor for the development of stomach cancer and peptic ulcer disease. In this study, we tested the hypothesis that H. pylori infection triggers alterations in gastric lipid composition.

Enhanced Fitness of a Helicobacter pylori Mutant in a Murine Model.

Helicobacter pylori genomes encode over 60 predicted outer membrane proteins (OMPs). Several OMPs in the Hop family act as adhesins, but the functions of most Hop proteins are unknown. To identify mutant strains exhibiting differential fitness compared to , we used a genetic barcoding method that allowed us to track changes in the proportional abundance of H.

Temporal Control of the Helicobacter pylori Cag Type IV Secretion System in a Mongolian Gerbil Model of Gastric Carcinogenesis.

The Cag type IV secretion system (T4SS) translocates the effector protein CagA and nonprotein bacterial constituents into host cells. In this study, we infected Mongolian gerbils with an strain in which expression of the operon (required for Cag T4SS activity) is controlled by a TetR/ system. Transcript levels of were significantly higher in gastric tissue from -infected animals receiving doxycycline-containing chow (to derepress Cag T4SS activity) than in tissue from infected control animals receiving drug-free chow.

T Cell Cytokines Impact Epithelial Cell Responses during Infection.

The goal of this is to highlight literature that demonstrates how cytokines made by T lymphocytes impact the gastric epithelium, especially during infection. These cytokines effect many of the diverse functions of the epithelium and the epithelium's interactions with The focal point of this will be on how T cell cytokines impact antimicrobial function and barrier function and how T cell cytokines influence the development and progression of cancer. Furthermore, the modulation of epithelial-derived chemokines by infection will be discussed.

Th17 Cells in Helicobacter pylori Infection: a Dichotomy of Help and Harm.

is a Gram-negative bacterium that infects the gastric epithelia of its human host. Everyone who is colonized with these pathogenic bacteria can develop gastric inflammation, termed gastritis. Additionally, a small proportion of colonized people develop more adverse outcomes, including gastric ulcer disease, gastric adenocarcinoma, or gastric mucosa-associated lymphoid tissue lymphoma.

Interleukin-21 (IL-21) Downregulates Dendritic Cell Cytokine Responses to Helicobacter pylori and Modulates T Lymphocyte IL-17A Expression in Peyer's Patches during Infection.

Interleukin-21 (IL-21), a cytokine produced by many subsets of activated immune cells, is critical for driving inflammation in several models. Using infection as a model for chronic mucosal infection, we previously published that IL-21 is required for the development of gastritis in response to infection. Concomitant with protection from chronic inflammation, -infected IL-21 mice exhibited limited Th1 and Th17 responses in their gastric mucosa.

Resolution of Gastric Cancer-Promoting Inflammation: A Novel Strategy for Anti-cancer Therapy.

The connection between inflammation and cancer was initially recognized by Rudolf Virchow in the nineteenth century. During the last decades, a large body of evidence has provided support to his hypothesis, and now inflammation is recognized as one of the hallmarks of cancer, both in etiopathogenesis and ongoing tumor growth. Infection with the pathogen Helicobacter pylori is the primary causal factor in 90% of gastric cancer (GC) cases.

Critical role of Interleukin 21 and T follicular helper cells in hypertension and vascular dysfunction.

T and B cells have been implicated in hypertension, but the mechanisms by which they produce a coordinated response is unknown. T follicular helper (Tfh) cells that produce interleukin 21 (IL21) promote germinal center (GC) B cell responses leading to immunoglobulin (Ig) production. Here we investigate the role of IL21 and Tfh cells in hypertension.

Protein kinase D mediates inflammatory responses of human placental macrophages to Group B Streptococcus.

Problem: During pregnancy, Group B Streptococcus (GBS) can infect fetal membranes to cause chorioamnionitis, resulting in adverse pregnancy outcomes. Macrophages are the primary resident phagocyte in extraplacental membranes. Protein kinase D (PKD) was recently implicated in mediating pro-inflammatory macrophage responses to GBS outside of the reproductive system.

genetic diversification in the Mongolian gerbil model.

requires genetic agility to infect new hosts and establish long-term colonization of changing gastric environments. In this study, we analyzed genetic adaptation in the Mongolian gerbil model. This model is of particular interest because -infected gerbils develop a high level of gastric inflammation and often develop gastric adenocarcinoma or gastric ulceration.

Signaling by two-component system noncognate partners promotes intrinsic tolerance to polymyxin B in uropathogenic Escherichia coli.

Bacteria use two-component systems (TCSs) to react appropriately to environmental stimuli. Typical TCSs comprise a sensor histidine kinase that acts as a receptor coupled to a partner response regulator that coordinates changes in bacterial behavior, often through its activity as a transcriptional regulator. TCS interactions are typically confined to cognate pairs of histidine kinases and response regulators.

TLR9 activation suppresses inflammation in response to Helicobacter pylori infection.

Helicobacter pylori (H. pylori) induces chronic gastritis in humans, and infection can persist for decades. One H.

Purine Biosynthesis Metabolically Constrains Intracellular Survival of Uropathogenic Escherichia coli.

The ability to de novo synthesize purines has been associated with the intracellular survival of multiple bacterial pathogens. Uropathogenic Escherichia coli (UPEC), the predominant cause of urinary tract infections, undergoes a transient intracellular lifestyle during which bacteria clonally expand into multicellular bacterial communities within the cytoplasm of bladder epithelial cells. Here, we characterized the contribution of the conserved de novo purine biosynthesis-associated locus cvpA-purF to UPEC pathogenesis.

Dietary Composition Influences Incidence of Helicobacter pylori-Induced Iron Deficiency Anemia and Gastric Ulceration.

Epidemiologic studies have provided conflicting data regarding an association between Helicobacter pylori infection and iron deficiency anemia (IDA) in humans. Here, a Mongolian gerbil model was used to investigate a potential role of H. pylori infection, as well as a possible role of diet, in H.

IL-17a and IL-22 Induce Expression of Antimicrobials in Gastrointestinal Epithelial Cells and May Contribute to Epithelial Cell Defense against Helicobacter pylori.

Helicobacter pylori colonization of the human stomach can lead to adverse clinical outcomes including gastritis, peptic ulcers, or gastric cancer. Current data suggest that in addition to bacterial virulence factors, the magnitude and types of immune responses influence the outcome of colonization. Specifically, CD4+ T cell responses impact the pathology elicited in response to H.

Helicobacter pylori Resists the Antimicrobial Activity of Calprotectin via Lipid A Modification and Associated Biofilm Formation.

Unlabelled: Helicobacter pylori is one of several pathogens that persist within the host despite a robust immune response. H. pylori elicits a proinflammatory response from host epithelia, resulting in the recruitment of immune cells which manifests as gastritis.

Helicobacter pylori adaptation in vivo in response to a high-salt diet.

Helicobacter pylori exhibits a high level of intraspecies genetic diversity. In this study, we investigated whether the diversification of H. pylori is influenced by the composition of the diet.