IL-8 is a key chemokine regulating neutrophil recruitment in a new mouse model of Shigella-induced colitis

J Immunol. 2004 Sep 15;173(6):4197-206. doi: 10.4049/jimmunol.173.6.4197.

Abstract

The lack of a mouse model of acute rectocolitis mimicking human bacillary dysentery in the presence of invasive Shigella is a major handicap to study the pathogenesis of the disease and to develop a Shigella vaccine. The inability of the mouse intestinal mucosa to elicit an inflammatory infiltrate composed primarily of polymorphonuclear leukocytes (PMN) may be due to a defect in epithelial invasion, in the sensing of invading bacteria, or in the effector mechanisms that recruit the PMN infiltrate. We demonstrate that the BALB/cJ mouse colonic epithelium not only can be invaded by Shigella, but also elicits an inflammatory infiltrate that, however, lacks PMN. This observation points to a major defect of mice in effector mechanisms, particularly the lack of expression of the CXC chemokine, IL-8. Indeed, this work demonstrates that the delivery of recombinant human IL-8, together with Shigella infection of the colonic epithelial surface, causes an acute colitis characterized by a strong PMN infiltrate that, by all criteria, including transcription profiles of key mediators of the innate/inflammatory response and histopathological lesions, mimics bacillary dysentery. This is a major step forward in the development of a murine model of bacillary dysentery.

MeSH terms

  • Animals
  • Chemokine CXCL1
  • Chemokine CXCL2
  • Chemokines / administration & dosage
  • Chemokines / biosynthesis
  • Chemokines / genetics
  • Chemokines, CXC
  • Colitis / immunology*
  • Colitis / microbiology
  • Colitis / pathology*
  • Colon / enzymology
  • Colon / immunology
  • Colon / microbiology
  • Colon / pathology
  • Cytokines / administration & dosage
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Disease Models, Animal
  • Dysentery, Bacillary / immunology*
  • Dysentery, Bacillary / microbiology
  • Dysentery, Bacillary / pathology*
  • Humans
  • Immunohistochemistry
  • Interleukin-8 / administration & dosage
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics
  • Interleukin-8 / physiology*
  • Intestinal Mucosa / enzymology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Kinetics
  • Lipopolysaccharides / metabolism
  • Male
  • Mice
  • Neutrophil Infiltration / immunology*
  • Neutrophils / immunology*
  • Neutrophils / microbiology
  • Neutrophils / pathology
  • Peroxidase / analysis
  • Peroxidase / biosynthesis
  • Recombinant Proteins / administration & dosage
  • Shigella flexneri / immunology*
  • Shigella flexneri / metabolism
  • Shigella flexneri / pathogenicity
  • Species Specificity
  • Transcription, Genetic / immunology

Substances

  • Chemokine CXCL1
  • Chemokine CXCL2
  • Chemokines
  • Chemokines, CXC
  • Cxcl1 protein, mouse
  • Cxcl2 protein, mouse
  • Cytokines
  • Interleukin-8
  • Lipopolysaccharides
  • Recombinant Proteins
  • keratinocyte-derived chemokines
  • Peroxidase