Targeting Host Sulphonyl Urea Receptor 2 Can Reduce Severity of Associated Gastritis.

Background And Aims: While most -infected individuals remain asymptomatic throughout their lifetime, in a significant proportion, the resulting severe chronic gastritis drives the development of gastric cancer. In this study, we examine a new therapeutic target, a host potassium channel regulatory subunit, SUR2 (encoded by ), with potential to protect against -associated diseases.

Methods: SUR2 gene (ABCC9) expression in human gastric biopsies was analyzed by quantitative polymerase chain reactions.

Natural cycles in South Pacific Gyre strength and the Southern Annular Mode.

The South Pacific Gyre (SPG) plays a vital role in regulating Southern Hemisphere climate and ecosystems. The SPG has been intensifying since the twentieth century due to changes in large scale wind forcing. These changes result from variability in the Southern Annular Mode (SAM), causing warming along the eastern SPG which affects local ecosystems.

Human pluripotent stem cell-derived macrophages host Mycobacterium abscessus infection.

Human macrophages are a natural host of many mycobacterium species, including Mycobacterium abscessus (M. abscessus), an emerging pathogen affecting immunocompromised and cystic fibrosis patients with few available treatments. The search for an effective treatment is hindered by the lack of a tractable in vitro intracellular infection model.

IL-33 promotes gastric tumour growth in concert with activation and recruitment of inflammatory myeloid cells.

Interleukin-33 (IL-33) is an IL-1 family cytokine known to promote T-helper (Th) type 2 immune responses that are often deregulated in gastric cancer (GC). IL-33 is overexpressed in human gastric tumours suggesting a role in driving GC progression although a causal link has not been proven. Here, we investigated the impact of IL-33 genetic deficiency in the well-characterized mouse model of GC.

Unconventional T Cell Immunity in the Lungs of Young Children with Cystic Fibrosis.

Background: People with Cystic Fibrosis (CF) develop pulmonary inflammation, chronic infection and structural lung damage early in life, with these manifestations being prevalent among preschool children and infants. While early immune events are believed to play critical roles in shaping the progression, severity and disease burden later in life, T cells and their subsets are poorly studied in the CF lung, particularly during the formative early stages of disease.

Methods: Using flow cytometry, we analyzed Mucosal Associated Invariant T (MAIT) cells, γδ T cells, and Natural Killer T (NKT)-like cells in bronchoalveolar lavage (BAL) samples from seventeen children with CF, aged two to six years old.

Systems serology detects functionally distinct coronavirus antibody features in children and elderly.

The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology.

A bacterial stimulation assay for bronchoalveolar lavage immune cells from young children with cystic fibrosis.

Cystic Fibrosis (CF) is primarily a progressive lung disease, characterized by chronic pulmonary infections with opportunistic pathogens. Such infections typically commence early in life, producing an inflammatory response marked by IL-8 chemokine production and neutrophilic infiltration, major contributory factors in CF progression. Studying this inflammation, especially early in life, is critical for developing new strategies for preventing or slowing disruption to the structural integrity of the CF airways.

Innate cell profiles during the acute and convalescent phase of SARS-CoV-2 infection in children.

Children have mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmed disease (COVID-19) compared to adults and the immunological mechanisms underlying this difference remain unclear. Here, we report acute and convalescent innate immune responses in 48 children and 70 adults infected with, or exposed to, SARS-CoV-2. We find clinically mild SARS-CoV-2 infection in children is characterised by reduced circulating subsets of monocytes (classical, intermediate, non-classical), dendritic cells and natural killer cells during the acute phase.

Synergistic effects of harvest and climate drive synchronous somatic growth within key New Zealand fisheries.

Fisheries harvest has pervasive impacts on wild fish populations, including the truncation of size and age structures, altered population dynamics and density, and modified habitat and assemblage composition. Understanding the degree to which harvest-induced impacts increase the sensitivity of individuals, populations and ultimately species to environmental change is essential to ensuring sustainable fisheries management in a rapidly changing world. Here we generated multiple long-term (44-62 years), annually resolved, somatic growth chronologies of four commercially important fishes from New Zealand's coastal and shelf waters.

Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19.

Compared to adults, children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have predominantly mild or asymptomatic infections, but the underlying immunological differences remain unclear. Here, we describe clinical features, virology, longitudinal cellular, and cytokine immune profile, SARS-CoV-2-specific serology and salivary antibody responses in a family of two parents with PCR-confirmed symptomatic SARS-CoV-2 infection and their three children, who tested repeatedly SARS-CoV-2 PCR negative. Cellular immune profiles and cytokine responses of all children are similar to their parents at all timepoints.

Influence of the MUC1 Cell Surface Mucin on Gastric Mucosal Gene Expression Profiles in Response to Infection in Mice.

The cell surface mucin MUC1 is an important host factor limiting ) pathogenesis in both humans and mice by providing a protective barrier and modulating mucosal epithelial and leukocyte responses. The aim of this study was to establish the time-course of molecular events in MUC1-modulated gene expression profiles in response to infection in wild type (WT) and MUC1-deficient mice using microarray-determined mRNA expression, gene network analysis and Ingenuity Pathway Analysis (IPA). A time-course over the first 72 h of infection showed significantly higher mucosal loads of bacteria at 8 h of infection in mice compared with WT, confirming its importance in the early stages of infection ( = 0.

Coordinate expression loss of and in gastric cancer via impairment of a glucocorticoid-responsive enhancer.

Gastrokines (GKNs) are anti-inflammatory proteins secreted by gastric epithelial (surface mucous and pit) cells, with their aberrant loss of expression causally linked to premalignant inflammation and gastric cancer (GC). Transcriptional mechanisms accounting for GKN expression loss have not been elucidated. Using human clinical cohorts, mouse transgenics, bioinformatics, and transfection/reporter assays, we report a novel mechanism of GKN gene transcriptional regulation and its impairment in GC.

A lack of role for antibodies in regulating Helicobacter pylori colonization and associated gastritis.

Background: Helicobacter pylori occupy a unique niche, located within the mucus layer lining the stomach, and attached to the apical surface of the gastric epithelium. As such, antibodies would be expected to play a major role in regulating infection and/or pathogenesis. However, experiments using antibody-deficient mice to study gastric helicobacter infection have yielded inconsistent results, although some pointed toward antibodies increasing colonization levels and decreasing gastritis severity.

Effect of MUC1 length polymorphisms on the NLRP3 inflammasome response of human macrophages.

Mucin 1 is a cell-membrane associated mucin, expressed on epithelial and immune cells that helps protect against pathogenic infections. In humans, MUC1 is highly polymorphic, predominantly due to the presence of a variable number tandem repeat (VNTR) region in the extracellular domain that results in MUC1 molecules of typically either short or long length. A genetic link is known between these MUC1 polymorphisms and inflammation-driven diseases, although the mechanism is not fully understood.

Overexpression of IL-11 promotes premalignant gastric epithelial hyperplasia in isolation from germline gp130-JAK-STAT driver mutations.

Expression of the cytokine IL-11 is elevated in human Helicobacter pylori infection and progressively increases with worsening gastric pathology. Additionally, IL-11 is required for tumor development in STAT3-dependent murine models of gastric cancer (GC) and, when administered acutely, causes resolving atrophic gastritis. However, it is unclear whether locally elevated IL-11 ligand expression can, in isolation from oncogenic gp130-JAK-STAT pathway mutations, initiate GC pathogenesis.

Status of vaccine research and development for Helicobacter pylori.

Gastric adenocarcinoma is globally the third leading cause of death due to malignancy, with the bulk of this disease burden being suffered by low and middle income countries (LMIC), especially in Asia. The majority of these cancers develop as a result of a chronic gastritis that arises in response to infection with the stomach-dwelling bacterium, Helicobacter pylori. A vaccine against this pathogen would therefore be a powerful tool for preventing gastric adenocarcinoma.

NOD1 is required for Helicobacter pylori induction of IL-33 responses in gastric epithelial cells.

Helicobacter pylori (H. pylori) causes chronic inflammation which is a key precursor to gastric carcinogenesis. It has been suggested that H.

Superoxide dismutase from Helicobacter pylori suppresses the production of pro-inflammatory cytokines during in vivo infection.

Background: Helicobacter pylori has undergone considerable adaptation to allow chronic persistence within the gastric environment. While H. pylori-associated diseases are driven by an excessive inflammation, severe gastritis is detrimental to colonization by this pathogen.

Mucin 1 protects against severe Streptococcus pneumoniae infection.

Streptococcus pneumoniae is a bacterial pathogen that commonly resides in the human nasopharynx, typically without causing any disease. However, in some cases these bacteria migrate from the nasopharynx to other sites of the body such as the lungs and bloodstream causing pneumonia and sepsis, respectively. This study used a mouse model of infection to investigate the potential role of Mucin 1 (MUC1), a cell membrane-associated glycoprotein known for playing a key barrier role at mucosal surfaces, in regulating this process.

Lack of small colony variants of Staphylococcus aureus from lower respiratory tract specimens.

Background: Small-colony variants (SCVs) of Staphylococcus aureus are associated with worse lung disease in children with Cystic Fibrosis (CF), exhibit a higher resistance to antibiotics and co-colonize more commonly with Pseudomonas aeruginosa compared to the normal phenotype. The prevalence of SCVs in lower airway specimens from children with CF is largely unknown.

Methods: Each visible morphotype of S.

Reduced PU.1 expression underlies aberrant neutrophil maturation and function in β-thalassemia mice and patients.

β-Thalassemia is associated with several abnormalities of the innate immune system. Neutrophils in particular are defective, predisposing patients to life-threatening bacterial infections. The molecular and cellular mechanisms involved in impaired neutrophil function remain incompletely defined.

Protease-activated Receptor 1 Plays a Proinflammatory Role in Colitis by Promoting Th17-related Immunity.

Background: Proteolytic cleavage of protease-activated receptor 1 (PAR1) can result in potent downstream regulatory effects on inflammation. Although PAR1 is expressed throughout the gastrointestinal tract and activating proteases are increased in inflammatory bowel disease, the effect of PAR1 activation on colitis remains poorly understood, and has not previously been studied in pediatric disease.

Methods: Expression of PAR1 and inflammatory cytokines in colonic biopsies from pediatric patients with Crohn's disease exhibiting active moderate to severe colitis was measured by quantitative PCR.

No evidence of a role for mitochondrial complex I in Helicobacter pylori pathogenesis.

Background: Complex I is the first enzyme complex in the mitochondrial respiratory chain, responsible for generating a large fraction of energy during oxidative phosphorylation. Recently, it has been identified that complex I deficiency can result in increased inflammation due to the generation of reactive oxygen species by innate immune cells. As a reduction in complex I activity has been demonstrated in human stomachs with atrophic gastritis, we investigated whether complex I deficiency could influence Helicobacter pylori pathogenesis.