Crohn's disease-associated adherent-invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly.
Ileal lesions in Crohn's disease (CD) patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC) able to invade and to replicate within intestinal epithelial cells. Recent genome-wide association studies have highlighted the autophagy pathway as being associated with CD risk. In the present study we investigated whether defects in autophagy enhance replication of commensal and pathogenic Escherichia coli and CD-associated AIEC. We show that functional autophagy limits intracellular AIEC replication and that a subpopulation of the intracellular bacteria is located within LC3-positive autophagosomes. In IRGM and ATG16L1 deficient cells intracellular AIEC LF82 bacteria have enhanced replication. Surprisingly autophagy deficiency did not interfere with the ability of intracellular bacteria to survive and/or replicate for any other E. coli strains tested, including non-pathogenic, environmental, commensal, or pathogenic strains involved in gastro enteritis. Together these findings demonstrate a central role for autophagy restraining Adherent-Invasive E. coli strains associated with ileal CD. AIEC infection in patients with polymorphisms in autophagy genes may have a significant impact on the outcome of intestinal inflammation.
Lapaquette
Pierre
P
Univ Clermont, Pathogénie Bactérienne Intestinale, USC-INRA, Clermont-Ferrand, France.
Glasser
Anne-Lise
AL
Huett
Alan
A
Xavier
Ramnik J
RJ
Darfeuille-Michaud
Arlette
A
D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003424:Crohn Disease / Q000235:genetics / Q000382:microbiology*; D004926:Escherichia coli / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D007413:Intestinal Mucosa / Q000382:microbiology; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D034741:RNA, Small Interfering
C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D034741:RNA, Small Interfering; D019204:GTP-Binding Proteins; C513539:IRGM protein, human