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Your search keyword '"Smith, Sionagh H."' showing total 23 results
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23 results on '"Smith, Sionagh H."'

12. Lawsonia intracellularis exploits β-catenin/Wnt and Notch signalling pathways during infection of intestinal crypt to alter cell homeostasis and promote cell proliferation

Author

Huan, Yang W, Bengtsson, Rebecca J, MacIntyre, Neil, Guthrie, Jack, Finlayson, Heather, Smith, Sionagh H, Archibald, Alan L, and Ait-Ali, Tahar

Subjects
Male, Swine, Lawsonia Bacteria, Sus scrofa, Gene Expression, lcsh:Medicine, Apoptosis, Random Allocation, Cell Signaling, Ileum, Medicine and Health Sciences, Genetics, Animals, Homeostasis, lcsh:Science, Wnt Signaling Pathway, beta Catenin, Cell Proliferation, Notch Signaling, Mammals, Staining, Mucin-2, Cell Death, Receptors, Notch, Caspase 3, lcsh:R, Organisms, DAPI staining, Biology and Life Sciences, SOX9 Transcription Factor, Cell Biology, Specimen preparation and treatment, Gastrointestinal Tract, Research and analysis methods, Desulfovibrionaceae Infections, Cell Processes, Vertebrates, Amniotes, Nuclear staining, Disease Progression, Female, lcsh:Q, Anatomy, Digestive System, Research Article, Signal Transduction
Abstract

Lawsonia intracellularis is an obligate intracellular bacterial pathogen that causes proliferative enteropathy (PE) in pigs. L. intracellularis infection causes extensive intestinal crypt cell proliferation and inhibits secretory and absorptive cell differentiation. However, the affected host upstream cellular pathways leading to PE are still unknown. β-catenin/Wnt signalling is essential in maintaining intestinal stem cell (ISC) proliferation and self-renewal capacity, while Notch signalling governs differentiation of secretory and absorptive lineage specification. Therefore, in this report we used immunofluorescence (IF) and quantitative reverse transcriptase PCR (RTqPCR) to examine β-catenin/Wnt and Notch-1 signalling levels in uninfected and L. intracellularis infected pig ileums at 3, 7, 14, 21 and 28 days post challenge (dpc). We found that while the significant increase in Ki67+ nuclei in crypts at the peak of L. intracellularis infection suggested enhanced cell proliferation, the expression of c-MYC and ASCL2, promoters of cell growth and ISC proliferation respectively, was down-regulated. Peak infection also coincided with enhanced cytosolic and membrane-associated β-catenin staining and induction of AXIN2 and SOX9 transcripts, both encoding negative regulators of β-catenin/Wnt signalling and suggesting a potential alteration to β-catenin/Wnt signalling levels, with differential regulation of the expression of its target genes. We found that induction of HES1 and OLFM4 and the down-regulation of ATOH1 transcript levels was consistent with the increased Notch-1 signalling in crypts at the peak of infection. Interestingly, the significant down-regulation of ATOH1 transcript levels coincided with the depletion of MUC2 expression at 14 dpc, consistent with the role of ATOH1 in promoting goblet cell maturation. The lack of significant change to LGR5 transcript levels at the peak of infection suggested that the crypt hyperplasia was not due to the expansion of ISC population. Overall, simultaneous induction of Notch-1 signalling and the attenuation of β-catenin/Wnt pathway appear to be associated with the inhibition of goblet cell maturation and enhanced crypt cell proliferation at the peak of L. intracellularis infection. Moreover, the apparent differential regulation of apoptosis between crypt and lumen cells together with the strong induction of Notch-1 signalling and the enhanced SOX9 expression along crypts 14 dpc suggest an expansion of actively dividing transit amplifying and/or absorptive progenitor cells and provide a potential basis for understanding the development and maintenance of PE.

Published
2017

15. Inflammatory infiltration into placentas of Neospora caninum challenged cattle correlates with clinical outcome of pregnancy

Author

Cantón, Germán J, primary, Katzer, Frank, additional, Maley, Stephen W, additional, Bartley, Paul M, additional, Benavides-Silván, Julio, additional, Palarea-Albaladejo, Javier, additional, Pang, Yvonne, additional, Smith, Sionagh H, additional, Rocchi, Mara S, additional, Buxton, David, additional, Innes, Elisabeth A, additional, and Chianini, Francesca, additional

Published
2014
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23. Review of methods for the detection of Lawsonia intracellularisinfection in pigs

Author

Campillo, Marta, Smith, Sionagh H., Gally, David L., and Opriessnig, Tanja

Abstract

Lawsonia intracellularisis an obligate intracellular bacterium associated with enteric disease in pigs. Clinical signs include weight loss, diarrhea, and, in some cases, sudden death. The hallmark lesion is the thickening of the intestinal mucosa caused by increased epithelial cell replication, known as proliferative enteropathy. The immune response to L. intracellularisis not well defined, and detection of the infection, especially in the early stages, is still a significant challenge. We review here the main approaches used to identify this important but poorly understood pathogen. Detection of L. intracellularisinfection as the cause of clinical disease is confounded by the high prevalence of the pathogen in many countries and that several other pathogens can produce similar clinical signs. A single L. intracellularis–specific ELISA and several amplification assays are available commercially to aid detection and surveillance, although histopathology remains the primary way to reach a conclusive diagnosis. There are major gaps in our understanding of L. intracellularispathogenesis, especially how the host responds to infection and the factors that drive infection toward different clinical outcomes. Knowledge of pathogenesis will increase the predictive value of antemortem tests to guide appropriate interventions, including identification and treatment of subclinically affected pigs in the early stages of disease, given that this important manifestation reduces pig productivity and contributes to the economic burden of L. intracellularisworldwide.

Published
2021
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