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Biomedical subjects

Brendan Wren

Publications and source records attributed to Brendan Wren.

4 recordsLinked to original sources

A plasmid immunization construct encoding urease B of Helicobacter pylori induces an antigen-specific antibody response and upregulates the expression of beta-defensins and IL-10 in the stomachs of immunized mice.

The objectives of this study were to investigate the efficacy of a prototype DNA immunization construct encoding the urease B subunit enzyme of Helicobacter pylori (H. pylori) for inducing adaptive and innate immune responses in mice immunized via intramuscular or subcutaneous routes and to further explore the adjuvant effects of the CpG motifs in the vector. Antibody, cytokine, and beta-defensin profiles were assessed in the stomachs of immunized animals: experiments were terminated 3 months after immunization because there was a significant increase in the anti-H. pylori urease B antibody response at Week 6 in mice immunized with the urease B construct. A long lasting expression of IL-10 mRNA was noted. Furthermore, a marked and sustained increase in the mRNA expression of beta-defensins was also observed, particularly beta1. This study demonstrates that an H. pylori urease B DNA construct can induce innate as well as adaptive immune responses in the stomachs of immunized mice. Upregulation of beta-defensin gene expression followed immunization and we believe that this is the first report of a DNA vaccine inducing innate anti-microbial responses. Such complex molecular interactions that modulate both innate and adaptive immune responses may be of critical importance in the control of mucosal pathogens, such as H. pylori.

Animals↗

Exploiting genome sequence: predictions for mechanisms of Campylobacter chemotaxis.

The genome sequence of Campylobacter jejuni NCTC 11168 reveals the presence of orthologues of the chemotaxis genes cheA, cheW, cheV, cheY, cheR and cheB, ten chemoreceptor genes and two aerotaxis genes. The presence of cheV and a response regulator domain in CheA, combined with the absence of a cheZ gene and the lack of a response regulator domain in CheB, reveals significant differences in the C. jejuni chemotaxis system compared with that found in other bacteria.

Bacterial Proteins↗

LsaA, an antigen involved in cell attachment and invasion, is expressed by Lawsonia intracellularis during infection in vitro and in vivo.

Lawsonia intracellularis has been identified recently as the etiological agent of proliferative enteropathies, which are characterized by intestinal epithelial hyperplasia and associated moderate immune responses. This disease complex has been reported in a broad range of animals, prevalently in pigs, and L. intracellularis has been linked with ulcerative colitis in humans. L. intracellularis is an obligate intracellular bacterium, and the pathogenic mechanisms used to cause disease are unknown. Using in vitro-grown organisms as a source of genomic DNA, we identified a Lawsonia gene which encodes a surface antigen, LsaA (for Lawsonia surface antigen), associated with attachment to and entry into cells. The deduced amino acid sequence of this protein showed some similarity to members of a novel protein family identified in a number of other bacterial pathogens but for which roles are not fully defined. Transcription of this gene was detected by reverse transcription-PCR in L. intracellularis grown in vitro in IEC18 cells and in bacteria present in ileal tissue from infected animals. Immunohistochemistry with specific monoclonal antibody and immunoblotting with sera from infected animals demonstrated that LsaA protein is synthesized by L. intracellularis during infection. Expression of this gene during infection in vitro and in vivo suggests that this surface antigen is involved during infection, and phenotypic analysis indicated a role during L. intracellularis attachment to and entry into intestinal epithelial cells

Adhesins, Bacterial↗