ORCID Profile
0000-0001-9115-8855
Current Organisation
University of Leeds
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Publisher: Public Library of Science (PLoS)
Date: 22-09-2016
Publisher: Public Library of Science (PLoS)
Date: 30-03-2012
Publisher: American Society for Clinical Investigation
Date: 04-2010
DOI: 10.1172/JCI41281
Publisher: Public Library of Science (PLoS)
Date: 26-07-2012
Publisher: Elsevier BV
Date: 10-2016
Publisher: American Society for Microbiology
Date: 03-2011
DOI: 10.1128/IAI.00633-10
Abstract: Optimal hepatic resistance to Leishmania donovani in mice requires the coordinated effort of a variety of leukocyte populations that together induce activation of local macrophages to a leishmanicidal state. Although nitric oxide and reactive oxygen intermediates are potent leishmanicidal effector molecules operating in the acquired phase of immunity, there have long been suggestions that other mechanisms of leishmanicidal activity exist. We recently discovered that Irf-7 regulates a novel innate leishmanicidal response in resident splenic macrophages that line the marginal zone. Here, we tested whether this mechanism also operates in Kupffer cells, the resident macrophage population of the liver and the major target for hepatic infection by L. donovani . Comparing the Kupffer cell responses in situ in B6 and B6. Irf-7 −/− mice, we found no evidence that Irf-7 affected amastigote uptake or early survival. However, we did find that Irf-7 -deficient mice had impaired acquired resistance to hepatic L. donovani infection. This phenotype was attributable to a reduction in the capacity of hepatic CD4 + T cells, NK cells, and NKT cells to produce gamma interferon (IFN-γ) and also to defective induction of NOS2 in infected Kupffer cells. Our data therefore add interferon regulatory factor 7 (IRF-7) to the growing list of interferon regulatory factors that have effects on downstream events in the acquired cellular immune response to nonviral pathogens.
Publisher: Elsevier BV
Date: 09-2006
DOI: 10.1053/J.GASTRO.2006.06.003
Abstract: Intestinal epithelial integrity and permeability is dependent on intercellular tight junction (TJ) complexes. How TJ integrity is regulated remains unclear, although phosphorylation and dephosphorylation of the integral membrane protein occludin is an important determinant of TJ formation and epithelial permeability. We have investigated the role intestinal intraepithelial lymphocytes (iIELs) play in regulating epithelial permeability in response to infection. Recombinant strains of Toxoplasma gondii were used to assess intestinal epithelial barrier function and TJ integrity in mice with intact or depleted populations of iIELs. Alterations in epithelial permeability were correlated with TJ structure and the state of phosphorylation of occludin. iIEL in vivo reconstitution experiments were used to identify the iIELs required to maintain epithelial permeability and TJ integrity. In the absence of gammadelta+ iIELs, intestinal epithelial barrier function and the ability to restrict epithelial transmigration of Toxoplasma and the unrelated intracellular bacterial pathogen Salmonella typhimurium was severely compromised. Leaky epithelium in gammadelta+ iIEL-deficient mice was associated with the absence of phosphorylation of serine residues of occludin and lack of claudin 3 and zona occludens-1 proteins in TJ complexes. These deficiencies were attributable to the absence of a single subset of gammadelta T-cell receptor (TCR-Vgamma7+) iIELs that, after reconstituting gammadelta iIEL-deficient mice, restored epithelial barrier function and TJ complexes, resulting in increased resistance to infection. These findings identify a novel role for gammadelta+ iIELs in maintaining TJ integrity and epithelial barrier function that have implications for understanding the pathogenesis of intestinal inflammatory diseases associated with disruption of TJ complexes.
Publisher: Elsevier BV
Date: 07-2011
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Jane Dalton.