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Crohn Disease: HELP
Articles by Cherrie-Lee N. Small
Based on 3 articles published since 2010
(Why 3 articles?)
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Between 2010 and 2020, Cherrie L. Small wrote the following 3 articles about Crohn Disease.
 
+ Citations + Abstracts
1 Article Acute Infectious Gastroenteritis Potentiates a Crohn's Disease Pathobiont to Fuel Ongoing Inflammation in the Post-Infectious Period. 2016

Small, Cherrie L / Xing, Lydia / McPhee, Joseph B / Law, Hong T / Coombes, Brian K. ·Michael G. DeGroote Institute for Infectious Disease Research, Hamilton, Ontario, Canada. · Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada. · Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada. ·PLoS Pathog · Pubmed #27711220.

ABSTRACT: Crohn's disease (CD) is a chronic inflammatory condition of diverse etiology. Exposure to foodborne pathogens causing acute gastroenteritis produces a long-term risk of CD well into the post-infectious period but the mechanistic basis for this ongoing relationship to disease onset is unknown. We developed two novel models to study the comorbidity of acute gastroenteritis caused by Salmonella Typhimurium or Citrobacter rodentium in mice colonized with adherent-invasive Escherichia coli (AIEC), a bacterial pathobiont linked to CD. Here, we show that disease activity in the post-infectious period after gastroenteritis is driven by the tissue-associated expansion of the resident AIEC pathobiont, with an attendant increase in immunopathology, barrier defects, and delays in mucosal restitution following pathogen clearance. These features required AIEC resistance to host defense peptides and a fulminant inflammatory response to the enteric pathogen. Our results suggest that individuals colonized by AIEC at the time of acute infectious gastroenteritis may be at greater risk for CD onset. Importantly, our data identify AIEC as a tractable disease modifier, a finding that could be exploited in the development of therapeutic interventions following infectious gastroenteritis in at-risk individuals.

2 Article Host defense peptide resistance contributes to colonization and maximal intestinal pathology by Crohn's disease-associated adherent-invasive Escherichia coli. 2014

McPhee, Joseph B / Small, Cherrie L / Reid-Yu, Sarah A / Brannon, John R / Le Moual, Hervé / Coombes, Brian K. ·Michael G. DeGroote Institute for Infectious Disease Research, Hamilton, Ontario, Canada Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada. · Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada. · Michael G. DeGroote Institute for Infectious Disease Research, Hamilton, Ontario, Canada Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada coombes@mcmaster.ca. ·Infect Immun · Pubmed #24866805.

ABSTRACT: Host defense peptides secreted by colonocytes and Paneth cells play a key role in innate host defenses in the gut. In Crohn's disease, the burden of tissue-associated Escherichia coli commonly increases at epithelial surfaces where host defense peptides concentrate, suggesting that this bacterial population might actively resist this mechanism of bacterial killing. Adherent-invasive E. coli (AIEC) is associated with Crohn's disease; however, the colonization determinants of AIEC in the inflamed gut are undefined. Here, we establish that host defense peptide resistance contributes to host colonization by Crohn's-associated AIEC. We identified a plasmid-encoded genomic island (called PI-6) in AIEC strain NRG857c that confers high-level resistance to α-helical cationic peptides and α- and β-defensins. Deletion of PI-6 sensitized strain NRG857c to these host defense molecules, reduced its competitive fitness in a mouse model of infection, and attenuated its ability to induce cecal pathology. This phenotype is due to two genes in PI-6, arlA, which encodes a Mig-14 family protein implicated in defensin resistance, and arlC, an OmpT family outer membrane protease. Implicit in these findings are new bacterial targets whose inhibition might limit AIEC burden and disease in the gut.

3 Article Persistent infection with Crohn's disease-associated adherent-invasive Escherichia coli leads to chronic inflammation and intestinal fibrosis. 2013

Small, Cherrie-Lee N / Reid-Yu, Sarah A / McPhee, Joseph B / Coombes, Brian K. ·Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5. ·Nat Commun · Pubmed #23748852.

ABSTRACT: Crohn's disease is a chronic inflammatory condition of the gastrointestinal tract in which alterations to the bacterial community contribute to disease. Adherent-invasive Escherichia coli are associated with human Crohn's disease; however, their role in intestinal immunopathology is unclear because of the lack of an animal model compatible with chronic timescales. Here we establish chronic adherent-invasive Escherichia coli infection in streptomycin-treated conventional mice (CD1, DBA/2, C3H, 129e and C57BL/6), enabling the study of host response and immunopathology. Adherent-invasive Escherichia coli induces an active T-helper 17 response, heightened levels of proinflammatory cytokines and fibrotic growth factors, with transmural inflammation and fibrosis. Depletion of CD8+ T cells increases caecal bacterial load, pathology and intestinal fibrosis in C57BL/6 mice, suggesting a protective role. Our findings provide evidence that chronic adherent-invasive Escherichia coli infections result in immunopathology similar to that seen in Crohn's disease. With this model, research into the host and bacterial genetics associated with adherent-invasive Escherichia coli-induced disease becomes more widely accessible.