Ronald R Marchelletta1, Melanie G Gareau1, Sharon Okamoto2, Donald G Guiney2, Kim E Barrett1, Joshua Fierer3. 1. Division of Gastroenterology. 2. Division of Infectious Diseases, University of California, San Diego, School of Medicine, La Jolla. 3. Division of Infectious Diseases, University of California, San Diego, School of Medicine, La Jolla Division of VA San Diego Healthcare System.
Abstract
BACKGROUND: Gastroenteritis is the most common manifestation of nontyphoidal Salmonella enterica infections, but little is known about the pathogenesis of diarrhea in this infection METHODS: To determine whether polymorphonuclear neutrophils (PMNs) are required for diarrhea for Salmonella colitis, we infected kanamycin-pretreated interleukin 8R (IL-8R) mutant mice and controls, both with nonmutant Slc11a1 (Nramp1, ItyR). We compared the 2 mouse strains for increases in fecal water content (diarrhea) 3 days after infection, changes in expression of ion transporters in colonic epithelial cells, proliferation of epithelial cells, and severity of infection as measured by colony-forming units (CFUs). RESULTS: The IL-8R knockout mice had fewer PMNs in the colon but the other variables we measured were unaffected except for an increase in CFUs in the colon. The pathologic changes in the cecum were similar in both groups except for the lack of PMNs in the IL-8R knockout mice. There was minimal damage to the colon more distally. CONCLUSIONS: In the early stage of Salmonella colitis, PMNs are not required for diarrhea or for the decrease in expression of colonic epithelial cell apical ion transporters. They contribute to defense against infection in the cecum but not extracolonically at this stage of Salmonella colitis. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
BACKGROUND: Gastroenteritis is the most common manifestation of nontyphoidal Salmonella enterica infections, but little is known about the pathogenesis of diarrhea in this infection METHODS: To determine whether polymorphonuclear neutrophils (PMNs) are required for diarrhea for Salmonella colitis, we infected kanamycin-pretreated interleukin 8R (IL-8R) mutant mice and controls, both with nonmutant Slc11a1 (Nramp1, ItyR). We compared the 2 mouse strains for increases in fecal water content (diarrhea) 3 days after infection, changes in expression of ion transporters in colonic epithelial cells, proliferation of epithelial cells, and severity of infection as measured by colony-forming units (CFUs). RESULTS: The IL-8R knockout mice had fewer PMNs in the colon but the other variables we measured were unaffected except for an increase in CFUs in the colon. The pathologic changes in the cecum were similar in both groups except for the lack of PMNs in the IL-8R knockout mice. There was minimal damage to the colon more distally. CONCLUSIONS: In the early stage of Salmonella colitis, PMNs are not required for diarrhea or for the decrease in expression of colonic epithelial cell apical ion transporters. They contribute to defense against infection in the cecum but not extracolonically at this stage of Salmonella colitis. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Entities:
Keywords:
Salmonella; colitis; diarrhea; epithelial cell; ion transporter; neutrophil
Authors: Simon Le Hello; Rene S Hendriksen; Benoît Doublet; Ian Fisher; Eva Møller Nielsen; Jean M Whichard; Brahim Bouchrif; Kayode Fashae; Sophie A Granier; Nathalie Jourdan-Da Silva; Axel Cloeckaert; E John Threlfall; Frederick J Angulo; Frank M Aarestrup; John Wain; François-Xavier Weill Journal: J Infect Dis Date: 2011-08-02 Impact factor: 5.226