Crohn's disease adherent-invasive Escherichia coli colonize and induce strong gut inflammation in transgenic mice expressing human CEACAM.
Abnormal expression of CEACAM6 is observed at the apical surface of the ileal epithelium in Crohn's disease (CD) patients, and CD ileal lesions are colonized by pathogenic adherent-invasive Escherichia coli (AIEC). We investigated the ability of AIEC reference strain LF82 to colonize the intestinal mucosa and to induce inflammation in CEABAC10 transgenic mice expressing human CEACAMs. AIEC LF82 virulent bacteria, but not nonpathogenic E. coli K-12, were able to persist in the gut of CEABAC10 transgenic mice and to induce severe colitis with reduced survival rate, marked weight loss, increased rectal bleeding, presence of erosive lesions, mucosal inflammation, and increased proinflammatory cytokine expression. The colitis depended on type 1 pili expression by AIEC bacteria and on intestinal CEACAM expression because no sign of colitis was observed in transgenic mice infected with type 1 pili-negative LF82-Delta fimH isogenic mutant or in wild-type mice infected with AIEC LF82 bacteria. These findings strongly support the hypothesis that in CD patients having an abnormal intestinal expression of CEACAM6, AIEC bacteria via type 1 pili expression can colonize the intestinal mucosa and induce gut inflammation. Thus, targeting AIEC adhesion to gut mucosa represents a new strategy for clinicians to prevent and/or to treat ileal CD.
Carvalho
Frédéric A
FA
Université Clermont 1, Pathogénie Bactérienne Intestinale, JE2526, Unité Sous Contrat Institut National de la Recherche Agronomique 2018, Clermont-Ferrand F-63001, France.
Barnich
Nicolas
N
Sivignon
Adeline
A
Darcha
Claude
C
Chan
Carlos H F
CH
Stanners
Clifford P
CP
Darfeuille-Michaud
Arlette
A
D018830:Adhesins, Escherichia coli / Q000502:physiology; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D001422:Bacterial Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D003092:Colitis / Q000209:etiology*; D003424:Crohn Disease / Q000382:microbiology*; D004926:Escherichia coli / Q000472:pathogenicity*; D036781:Fimbriae Proteins / Q000502:physiology; D058851:GPI-Linked Proteins; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic
D018830:Adhesins, Escherichia coli; D015703:Antigens, CD; C504117:CEACAM6 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; C058769:fimH protein, E coli; D036781:Fimbriae Proteins