title: IL-8 is a key chemokine regulating neutrophil recruitment in a new mouse model of Shigella-induced colitis.
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.
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Institut National de la Santé et de la Recherche Médicale U389, Institut Pasteur, Paris, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Singer
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Sansonetti
mesh_terms: D000818:Animals; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics; D019743:Chemokines, CXC; D003092:Colitis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D003106:Colon / Q000201:enzymology / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016207:Cytokines / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D004405:Dysentery, Bacillary / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007413:Intestinal Mucosa / Q000201:enzymology / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D009195:Peroxidase / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000008:administration & dosage; D012763:Shigella flexneri / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D013045:Species Specificity; D014158:Transcription, Genetic / Q000276:immunology
chemical_list: D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D016207:Cytokines; D016209:Interleukin-8; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; C074302:keratinocyte-derived chemokines; D009195:Peroxidase