The Immune Memory Response of In Vitro-Polarised Th1, Th2, and Th17 Cells in the Face of Ovalbumin-Transgenic in a Mouse Model.

Th1 and Th2 cytokines determine the outcome of infection and immune protection depends mainly on memory T cells induced during vaccination. This largely hinges on the nature and type of memory T cells produced. In this study, transgenic strains expressing membrane-associated ovalbumin (mOVA) and soluble ovalbumin (sOVA) were used as a model to study whether fully differentiated Th1/Th2 and Th17 cells can recall immune memory and tolerate pathogen manipulation.

Measuring the Manipulation of T Helper Immune Responses by .

uses different mechanisms to escape its host's immunity. Understanding the ability of memory T cells to withstand this pathogen's manipulation is important for the development of effective vaccines against this immunomodulatory pathogen. In this study, ovalbumin (OVA) transgenic is used as a tool to investigate whether fully differentiated Th1, Th2 and Th17 cells are able to withstand pathogen manipulation.

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.

Recognition of Schistosoma mansoni egg-expressed ovalbumin by T cell receptor transgenic mice.

Schistosoma mansoni eggs can influence immune responses directed at them, and the mechanisms by which this is achieved are being unravelled. Going towards, developing effective tools for the study of how S. mansoni influences naïve T cells, we have developed S.

Investigating immune responses to parasites using transgenesis.

Parasites comprise diverse and complex organisms, which substantially impact human and animal health. Most parasites have complex life-cycles, and by virtue of co-evolution have developed multifaceted, often life-cycle stage-specific relationships with the immune system of their hosts. The complexity in the biology of many parasites often limits our knowledge of parasite-specific immune responses, to in vitro studies only.

Mucosal-Associated Invariant T Cells Augment Immunopathology and Gastritis in Chronic Infection.

Mucosal-associated invariant T (MAIT) cells produce inflammatory cytokines and cytotoxic granzymes in response to by-products of microbial riboflavin synthesis. Although MAIT cells are protective against some pathogens, we reasoned that they might contribute to pathology in chronic bacterial infection. We observed MAIT cells in proximity to bacteria in human gastric tissue, and so, using MR1-tetramers, we examined whether MAIT cells contribute to chronic gastritis in a mouse SS1 infection model.

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.

A T cell-specific knockout reveals an important role for protease-activated receptor 2 in lymphocyte development.

Activation of protease-activated receptor-2 (PAR) expressed by T cells has been linked to the bone loss associated with periodontitis. We generated PAR conditional-null mice and crossed these with mice expressing Cre recombinase under control of the Lck proximal promoter, to produce T cell-specific PAR-null mice in order to further study the cellular mechanism involved in periodontitis. Here we report that efficient deletion of PAR in thymocytes isolated from T cell-specific PAR-null mice resulted in thymic and splenic hypoplasia and a reduction in the cells of the cortex and a loss of distinction between the cortex and the medulla of the thymus.

The MUC1 mucin protects against Helicobacter pylori pathogenesis in mice by regulation of the NLRP3 inflammasome.

Objectives: The mucin MUC1, best known for providing an epithelial barrier, is an important protective host factor in both humans and mice during Helicobacter pylori pathogenesis. This study aimed to identify the long-term consequences of MUC1 deficiency on H. pylori pathogenesis and the mechanism by which MUC1 protects against H.

Exploring local immune responses to vaccines using efferent lymphatic cannulation.

The early stages of the induction of a primary immune response to a vaccine can shape the overall quality of the immune memory generated and hence affect the success of the vaccine. This early interaction between a vaccine and the immune system occurs first at the site of vaccination and can be explored using afferent cannulation. Subsequently, the vaccine and adjuvant activates the local draining lymph node.

Omega-1 knockdown in Schistosoma mansoni eggs by lentivirus transduction reduces granuloma size in vivo.

Schistosomiasis, one of the most important neglected tropical diseases worldwide, is caused by flatworms (blood flukes or schistosomes) that live in the bloodstream of humans. The hepatointestinal form of this debilitating disease results from a chronic infection with Schistosoma mansoni or Schistosoma japonicum. No vaccine is available to prevent schistosomiasis, and treatment relies predominantly on the use of a single drug, praziquantel.

Recombinant herpesvirus glycoprotein G improves the protective immune response to Helicobacter pylori vaccination in a mouse model of disease.

Alphaherpesviruses, which have co-evolved with their hosts for more than 200 million years, evade and subvert host immune responses, in part, by expression of immuno-modulatory molecules. Alphaherpesviruses express a single, broadly conserved chemokine decoy receptor, glycoprotein G (gG), which can bind multiple chemokine classes from multiple species, including human and mouse. Previously, we demonstrated that infection of chickens with an infectious laryngotracheitis virus (ILTV) mutant deficient in gG resulted in altered host immune responses compared to infection with wild-type virus.

Key host-pathogen interactions for designing novel interventions against Helicobacter pylori.

Helicobacter pylori can persist in the stomach of infected individuals for life, in the face of chronic inflammation and low pH. Efforts to develop vaccines have largely failed and, in the wake of emerging antibiotic resistance, novel therapeutic approaches must be considered. This review will discuss recent salient findings of host factors that modulate inflammatory responses to H.

Helicobacter pylori thiolperoxidase as a protective antigen in single- and multi-component vaccines.

Helicobacter pylori is an important pathogen of the human stomach, and the development of a protective vaccine has been an enticing goal for many years. The H. pylori antioxidant enzymes superoxide dismutase (SOD) and catalase (KatA) have been shown to be protective as vaccine antigens in mice, demonstrating that the organism's antioxidant enzyme system is a fruitful target for vaccine development.

Increased Helicobacter felis colonization in male 129/Sv mice fails to suppress gastritis.

Development of the pathologies associated with Helicobacter pylori infection, most seriously gastric adenocarcinoma, are a consequence of chronic inflammation, which both host and pathogen go to some lengths to minimize. Recently, we presented evidence that H. pylori can suppress the development of inflammation in its immediate microenvironment in the gastric mucosa of 129/Sv mice.

Helicobacter pylori defense against oxidative attack.

Helicobacter pylori is a microaerophilic, gram-negative pathogen of the human stomach. Despite the chronic active gastritis that develops following colonization, H. pylori is able to persist unharmed in the stomach for decades.

Localized suppression of inflammation at sites of Helicobacter pylori colonization.

While gastric adenocarcinoma is the most serious consequence of Helicobacter pylori infection, not all infected persons develop this pathology. Individuals most at risk of this cancer are those in whom the bacteria colonize the acid-secreting region of the stomach and subsequently develop severe inflammation in the gastric corpus. It has been reported anecdotally that male mice become infected with greater numbers of H.

Did transmission of Helicobacter pylori from humans cause a disease outbreak in a colony of Stripe-faced Dunnarts (Sminthopsis macroura)?

Since the discovery that Helicobacter pylori causes a range of pathologies in the stomachs of infected humans, it has become apparent that Helicobacters are found in a diverse range of animal species where they are frequently associated with disease. In 2003 and 2004, there were two outbreaks of increased mortality associated with gastric bleeding and weight-loss in a captive colony of the Australian marsupial, the Stripe-faced Dunnart (Sminthopsis macroura). The presence of gastric pathology led to an investigation of potential Helicobacter pathogenesis in these animals.

Evaluation of superoxide dismutase from Helicobacter pylori as a protective vaccine antigen.

Helicobacter pylori, the major cause of gastric cancer, have mechanisms that allow colonization of the inhospitable gastric mucosa, including enzymes such as superoxide dismutase (SOD) which protect against reactive oxygen species. As SOD is essential for in vivo colonization, we theorized it might constitute a viable vaccine target. H.

MUC1 limits Helicobacter pylori infection both by steric hindrance and by acting as a releasable decoy.

The bacterium Helicobacter pylori can cause peptic ulcer disease, gastric adenocarcinoma and MALT lymphoma. The cell-surface mucin MUC1 is a large glycoprotein which is highly expressed on the mucosal surface and limits the density of H. pylori in a murine infection model.

M-cell targeting of whole killed bacteria induces protective immunity against gastrointestinal pathogens.

As the majority of human pathogens infect via a mucosal surface, delivery of killed vaccines by mucosal routes could potentially improve protection against many such organisms. Our ability to develop effective killed mucosal vaccines is inhibited by a lack of adjuvants that are safe and effective in humans. The Ulex europaeus agglutinin I (UEA-I) lectin specifically binds M cells lining the murine gastrointestinal tract.

Systemic immunization with unadjuvanted whole Helicobacter pylori protects mice against heterologous challenge.

Background: Adjuvant-free vaccines have many benefits, including decreased cost and toxicity. We examined the protective effect of systemic vaccination with adjuvant-free formalin-fixed Helicobacter pylori or bacterial lysate and the ability of this vaccine to induce protection against heterologous challenge.

Materials And Methods: Mice were vaccinated subcutaneously with H.

Muc1 limits Helicobacter felis binding to gastric epithelial cells but does not limit colonization and gastric pathology following infection.

Background: The mucin Muc1 is constitutively expressed by the gastric mucosa and is likely the first point of direct contact between the host stomach and the adherent pathogens. The expression of Muc1 has been shown to limit colonization of mice by Helicobacter pylori, known to adhere to the gastric epithelium, as well as associated pathology. However, the potential role of this mucin against nonadherent Helicobacter has not been previously studied.

Muc1 mucin limits both Helicobacter pylori colonization of the murine gastric mucosa and associated gastritis.

Background & Aims: The MUC1 mucin is expressed on the cell surface of epithelial cells lining the gastric mucosa. Epidemiologic studies suggest that functional allelic variations in the MUC1 gene may play a role in human susceptibility to Helicobacter pylori-associated pathologies, including gastric adenocarcinoma. We have evaluated the impact of Muc1 expression on the colonization and pathogenesis of gastric Helicobacter infections.

Helicobacter pylori flagella: antigenic profile and protective immunity.

Reproducible induction of sterilizing immunity, essential for an effective Helicobacter pylori vaccine, remains elusive. As motility is essential for gastric colonization by Helicobacter, we evaluated whether a vaccine targeting flagella induces improved protection. Mice immunized with a vaccine enriched for H.