Anti-Toxin Responses to Natural Enterotoxigenic (ETEC) Infection in Adults and Children in Bangladesh.

A sero-epidemiology study was conducted in Dhaka, Bangladesh between January 2020 and February 2021 to assess the immune responses to ETEC infection in adults and children. (1) Background: Enterotoxigenic infection is a main cause of diarrheal disease in endemic countries. The characterization of the immune responses evoked by natural infection can guide vaccine development efforts.

A novel precision-serology assay for SARS-CoV-2 infection based on linear B-cell epitopes of Spike protein.

Introduction: The COVID-19 pandemic illustrates the need for serology diagnostics with improved accuracy. While conventional serology based on recognition of entire proteins or subunits thereof has made significant contribution to the antibody assessment space, it often suffers from sub-optimal specificity. Epitope-based, high-precision, serology assays hold potential to capture the high specificity and diversity of the immune system, hence circumventing the cross-reactivity with closely related microbial antigens.

Analysis of the Viable Microbiota and Helicobacter pylori Transcriptome in Gastric Infection and Early Stages of Carcinogenesis.

Emerging evidence shows that the human microbiota plays a larger role in disease progression and health than previously anticipated. , the causative agent of gastric cancer and duodenal and gastric ulcers, was early associated with gastric disease, but it has also been proposed that the accompanying microbiota in -infected individuals might affect disease progression and gastric cancer development. In this study, the composition of the transcriptionally active microbial community and gene expression were determined using metatranscriptomic RNA sequencing of stomach biopsy specimens from individuals with different infection statuses and premalignant tissue changes.

Identification of a Latin American-specific BabA adhesin variant through whole genome sequencing of Helicobacter pylori patient isolates from Nicaragua.

Background: Helicobacter pylori (H. pylori) is one of the most common bacterial infections in humans and this infection can lead to gastric ulcers and gastric cancer. H.

CD4 regulatory T cells in gastric cancer mucosa are proliferating and express high levels of IL-10 but little TGF-β.

Background: An increase of regulatory T cells, defined as CD25- and/or FOXP3-expressing CD4 T cells, within tumors has been reported in several studies. Tregs promote tumor growth by modulating the antitumor immune response, mainly through inhibition of T-cell-mediated tumor cell killing: this has been suggested to be dependent on IL-10 and/or TGF-β. In stomach cancer, the mechanisms behind the accumulation of Tregs in tumor tissue has not been fully elucidated, and neither has Treg gene expression in situ.

Th1 and Th17 responses to Helicobacter pylori in Bangladeshi infants, children and adults.

Both Th1 and Th17 cells are important components of the immune response to Helicobacter pylori (Hp) in adults, but less is known about T cell responses to Hp during early childhood, when the infection is often acquired. We investigated Th1 and Th17 type responses to Hp in adults, children and infants in Bangladesh, where Hp is highly endemic. IL-17 and IFN-γ mRNA levels in gastric biopsies from Hp-infected Bangladeshi adults were analyzed and compared to levels in infected and uninfected Swedish controls.

Transcriptome signatures in Helicobacter pylori-infected mucosa identifies acidic mammalian chitinase loss as a corpus atrophy marker.

Background: The majority of gastric cancer cases are believed to be caused by chronic infection with the bacterium Helicobacter pylori, and atrophic corpus gastritis is a predisposing condition to gastric cancer development. We aimed to increase understanding of the molecular details of atrophy by performing a global transcriptome analysis of stomach tissue.

Methods: Biopsies from patients with different stages of H.

DC-LAMP+ dendritic cells are recruited to gastric lymphoid follicles in Helicobacter pylori-infected individuals.

Infection with Helicobacter pylori is associated with development of ulcer disease and gastrointestinal adenocarcinoma. The infection leads to a large infiltration of immune cells and the formation of organized lymphoid follicles in the human gastric mucosa. Still, the immune system fails to eradicate the bacteria, and the substantial regulatory T cell (Treg) response elicited is probably a major factor permitting bacterial persistence.

Stronger T cell immunogenicity of ovalbumin expressed intracellularly in Gram-negative than in Gram-positive bacteria.

This study aimed to clarify whether Gram-positive (G+) and Gram-negative (G-) bacteria affect antigen-presenting cells differently and thereby influence the immunogenicity of proteins they express. Lactobacilli, lactococci and Escherichia coli strains were transformed with plasmids conferring intracellular ovalbumin (OVA) production. Murine splenic antigen presenting cells (APCs) were pulsed with washed and UV-inactivated OVA-producing bacteria, control bacteria, or soluble OVA.

Evolution of the human gastrokine locus and confounding factors regarding the pseudogenicity of GKN3.

In a screen for genes expressed specifically in gastric mucous neck cells, we identified GKN3, the recently discovered third member of the gastrokine family. We present confirmatory mouse data and novel porcine data showing that mouse GKN3 expression is confined to mucous cells of the corpus neck and antrum base and is prominently expressed in metaplastic lesions. GKN3 was proposed originally to be expressed in some human populations and a pseudogene in others.

Immune responses against Helicobacter pylori in gastric cancer patients and in risk groups for gastric cancer.

Background: It has previously been reported that weak serum IgG but elevated IgA antibody responses against H. pylori may be associated with risk of gastric cancer (GC) development. To search for potential immunologic markers for GC, we analyzed antibody responses against H.

Human gastric mucins differently regulate Helicobacter pylori proliferation, gene expression and interactions with host cells.

Helicobacter pylori colonizes the mucus niche of the gastric mucosa and is a risk factor for gastritis, ulcers and cancer. The main components of the mucus layer are heavily glycosylated mucins, to which H. pylori can adhere.

Accumulation of CCR4⁺CTLA-4 FOXP3⁺CD25(hi) regulatory T cells in colon adenocarcinomas correlate to reduced activation of conventional T cells.

Background: Colorectal cancer usually gives rise to a specific anti-tumor immune response, but for unknown reasons the resulting immunity is not able to clear the tumor. Recruitment of activated effector lymphocytes to the tumor is important for efficient anti-tumor responses, while the presence of regulatory T cells (Treg) down-modulate tumor-specific immunity. We therefore aimed to determine homing mechanisms and activation stage of Treg and effector T cell infiltrating colon tumors compared to cells from the unaffected mucosa in patients suffering from colon adenocarcinoma.

Impaired IFN-γ production after stimulation with bacterial components by natural killer cells from gastric cancer patients.

Gastric adenocarcinoma is a major health problem world-wide, as this is the second most common cause of cancer death in the world. It has been estimated that infection by Helicobacter pylori cause at least half of the gastric cancers. Previously, we have demonstrated that H.

CD8- natural killer cells are greatly enriched in the human gastrointestinal tract and have the capacity to respond to bacteria.

Natural killer (NK) cells can be activated to produce IFN-gamma by lysate from Helicobacter pylori in combination with IL-12. Furthermore, NK cells in the gastrointestinal mucosa are likely to encounter H. pylori as well as other bacteria and may play a role in the mucosal innate immune defense.

Interferon-gamma secretion is induced in IL-12 stimulated human NK cells by recognition of Helicobacter pylori or TLR2 ligands.

Helicobacter pylori induce a chronic inflammation in the human gastric mucosa characterized by increased production of interferon-gamma (IFN-γ). The presence of natural killer (NK) cells in the human gastric mucosa and the ability of NK cells to produce IFN-γ suggest an important role of NK cells in the immune response directed towards H. pylori infection.

FOXP3-expressing CD4(+) T-cell numbers increase in areas of duodenal gastric metaplasia and are associated to CD4(+) T-cell aggregates in the duodenum of Helicobacter pylori-infected duodenal ulcer patients.

Background: We have previously demonstrated that Helicobacter pylori infection is associated with an increased number of CD4(+)CD25(high) regulatory T cells in the gastric and duodenal mucosa. In this study, we determined the number and localization of CD4(+) cells expressing the regulatory T-cell-specific transcription factor FOXP3 in the antrum and duodenum of duodenal ulcer patients, asymptomatic carriers, and uninfected individuals. We also determined gene expression levels of FOXP3 as well as anti- and proinflammatory cytokines before and after H.

Cholera caused by Vibrio cholerae O1 induces T-cell responses in the circulation.

Considerable effort is being made to understand the acute and memory antibody responses in natural cholera infection, while rather less is known about the roles of cellular immune responses involving T and B lymphocytes. We studied responses in adult patients hospitalized with cholera caused by Vibrio cholerae O1. Peripheral blood mononuclear cells from patients (n = 15) were analyzed by flow cytometry after stimulation with V.

Human IgA-secreting cells induced by intestinal, but not systemic, immunization respond to CCL25 (TECK) and CCL28 (MEC).

Organ-specific homing of lymphoid cells depends on the expression of tissue-specific adhesion molecules and production of specific chemokines. CCL25 (TECK) and CCL28 (MEC) have been reported to direct circulating memory/effector B cells to mucosal tissues. Here, we examined if differential responsiveness to mucosal and systemic chemokines could explain the differential migration pattern of circulating human antibody-secreting cells (ASC), induced by mucosal and systemic immunization.

The local and systemic T-cell response to Helicobacter pylori in gastric cancer patients is characterised by production of interleukin-10.

Helicobacter pylori causes a life-long infection that may lead to development of gastric adenocarcinoma (GC) and thereby cause major worldwide health problems. The present study was designed to study whether those that develop GC have an altered immune response to H. pylori compared to individuals that remain asymptomatic.

CD4+ CD25high regulatory T cells reduce T cell transendothelial migration in cancer patients.

Cell-mediated immunity is thought to be the main mechanism of anti-tumour responses of the host, but it is not known if cancer disease affects T cell recruitment from blood to tissues. Therefore, we compared Heliobacter pylori-induced T cell transendothelial migration (TEM) in H. pylori-infected gastric carcinoma patients, colon and lung carcinoma patients and healthy volunteers.

Oral tolerance induction with antigen conjugated to cholera toxin B subunit generates both Foxp3+CD25+ and Foxp3-CD25- CD4+ regulatory T cells.

Oral administration of Ag coupled to cholera toxin B subunit (CTB) efficiently induces peripheral immunological tolerance. We investigated the extent to which this oral tolerance is mediated by CD25+CD4+ regulatory T cells (T(reg)). We found that total T(reg), KJ1-26+ T(reg) and CTLA-4+ T(reg) were all increased in Peyer's patches, mesenteric lymph nodes, and, to a lesser extent, in spleen of mice after intragastric administration of OVA/CTB conjugate, which also increased TGF-beta in serum.

Function and recruitment of mucosal regulatory T cells in human chronic Helicobacter pylori infection and gastric adenocarcinoma.

CD4(+)CD25(high) FOXP3-expressing regulatory T cells (Treg) can suppress immune responses to infections and tumors, thereby promoting microbial persistence and tumor progression. However, little is known about the phenotype and function of human mucosal Treg. Therefore, we analyzed the suppressive activity and homing phenotype of Treg in gastric mucosa of Helicobacter pylori-infected gastric adenocarcinoma patients.

Identification of protein expression signatures associated with Helicobacter pylori infection and gastric adenocarcinoma using recombinant antibody microarrays.

Antibody microarray based technology is a powerful emerging tool in proteomics, target discovery, and differential analysis. Here, we report the first study where recombinant antibody fragments have been used to construct large scale antibody microarrays, composed of 127 different antibodies against mostly immunoregulatory antigens. The arrays were based on single framework recombinant antibody fragments (SinFabs) designed for high on-chip stability and functionality and were used for the analysis of malignant and normal stomach tissue samples from Helicobacter pylori-positive and -negative patients.