Biomedical subjects

Maureen L Drakes

Publications and source records attributed to Maureen L Drakes.

4 recordsLinked to original sources

PubMed2006

Regulation of murine dendritic cell immune responses by Helicobacter felis antigen.

Helicobacter infections are present in approximately 50% of humans, causing severe illnesses such as gastritis and malignancies. Dendritic cells (DC) are critical antigen-presenting cells which link innate and adaptive immune responses. The mechanism of dendritic cell regulation in Helicobacter-induced gastritis is poorly understood. These studies characterized DC isolated from the lamina propria of Helicobacter-infected mice and analyzed innate and adaptive immune responses elicited by Helicobacter antigen (Ag)-pulsed DC. The presence of DC was elevated in the gastric lamina propria infiltrate of infected mice in comparison with controls. After treatment with Helicobacter felis Ag, DC were polarized to secrete interleukin-6 as the dominant cytokine. In the presence of DC and Helicobacter Ag, responder allogeneic T cells in culture exhibited limited cell division. We suggest that the response of DC and T cells to Helicobacter Ag is critical to the chronic persistence of Helicobacter-induced gastritis.

Animals↗

PubMed2005

Colon lamina propria dendritic cells induce a proinflammatory cytokine response in lamina propria T cells in the SCID mouse model of colitis.

Intestinal immune responses are normally regulated to maintain a state of immune balance. Dendritic cells (DC) are antigen-presenting cells, which induce immune responses against microbes and other stimuli and are key players in the regulation of tolerance in the gut. These cells influence the differentiation of cytokine responses in T cells, and in the gut, in particular, such interactions may be critical to the course of inflammatory bowel disease (IBD). Using the CD45RBhi CD4+ T cell-reconstituted severe combined immunodeficient mouse model of colitis, we investigated the ability of isolated colon DC to stimulate immune responses in syngeneic and allogeneic spleen CD4+ T cells, as well as in colon T cells isolated from the same tissue as DC in IBD mice. We found that the frequency of DC in IBD mice colons and spleens was elevated in comparison with control mice, but colon and spleen DC exhibited different phenotypic and functional properties. Colon DC stimulated significantly higher levels of interferon-gamma and interleukin-6 when cocultured with autologous colon T cells than in cocultures with syngeneic or allogeneic spleen T cells. These data suggest that in the IBD colon, DC-T cell interactions may create conditions with an abundance of proinflammatory cytokines, which favor the inflammatory state.

Animals↗

PubMed2005

Eradication of Helicobacter pylori and resolution of gastritis in the gastric mucosa of IL-10-deficient mice.

BACKGROUND: Helicobacter pylori has been shown to induce pronounced gastric inflammation in the absence of interleukin-10 (IL-10) by 6 weeks post inoculation. The ability of IL-10(-/-) mice to eradicate H. pylori has not been demonstrated, possibly due to early sacrifice. Therefore, the long-term effect of enhanced gastritis on H. pylori colonization was determined in IL-10(-/-) mice. METHODS: C57BL/6 and IL-10(-/-) mice were infected with H. pylori and assessed for the degree of gastritis, bacterial load, and in vitro T-cell recall response at 4 and 16 weeks of infection. RESULTS: Infection of IL-10(-/-) mice resulted in significantly more severe gastritis than wild-type control mice and eradication of H. pylori by 4 weeks post inoculation. By 16 weeks, the level of gastritis in IL-10(-/-) was reduced to the levels observed in wild-type mice. Splenocytes from IL-10(-/-) mice were prone to produce significantly greater amounts of IFN-gamma than wild-type mice when stimulated with bacterial antigens. CONCLUSIONS: These results indicate that the host is capable of spontaneously eradicating H. pylori from the gastric mucosa when inflammation is elevated beyond the chronic inflammation induced in wild-type mice, and that the gastritis dissipates following bacterial eradication. Additionally, these data provide support for a model of gastrointestinal immunity in which naturally occurring IL-10-producing regulatory T cells modulate the host response to gastrointestinal bacteria.

Animals↗

PubMed2004

Helicobacter infection: pathogenesis.

PURPOSE OF REVIEW: Helicobacter pylori remains one of the world's most prevalent bacterial pathogens, often causing gastritis, peptic ulcer disease, gastric mucosa-associated lymphatic tissue lymphoma, or gastric adenocarcinoma. Elucidation of H. pylori virulence mechanisms and characteristics of the host that contribute to pathogenesis will facilitate the development of both pharmacologic and immunologic therapies. RECENT FINDINGS: The functional status of the outer inflammatory protein A may have predictive value for duodenal ulcer, and host alleles for interleukin-1beta, interleukin-1R, tumor necrosis factor-alpha, and interleukin-10 correlate with increased risk for gastric cancer. H. pylori vacuolating cytotoxin A and cytotoxin-associated gene A protein interact with multiple host proteins, although downstream signaling events need further characterization. It does appear however, that CagA may participate in a negative feedback loop on Src family kinases to prevent further phosphorylation of CagA. Several models, including delayed type hypersensitivity in immune mice, and spontaneous clearance of H. pylori from interleukin-10 and phagocyte oxidase mice, provide evidence that severe inflammation may be sufficient to eradicate H. pylori. The strategies used by H. pylori to avoid the inflammatory response are also becoming clearer. H. pylori remains viable when internalized by epithelial cells, and it remains viable in macrophage phagosomes by inhibiting phagosome maturation. Additionally, H. pylori may regulate the host immune response through activation of dendritic cells and CD25 regulatory T cells, and it may direct immunosuppression of T cells. SUMMARY: Helicobacter pylori virulence is accomplished through many mechanisms, including vacuolating cytotoxin A and CagA activities, and may be predicted based on bacterial and host genotypes. Ultimately, H. pylori persistence may depend on its success in downregulating the inflammatory response.

Journal Article↗