Small Intestine Early Innate Immunity Response during Intestinal Colonization by Escherichia coli Depends on Its Extra-Intestinal Virulence Status.
Uropathogenic Escherichia coli (UPEC) strains live as commensals in the digestive tract of the host, but they can also initiate urinary tract infections. The aim of this work was to determine how a host detects the presence of a new UPEC strain in the digestive tract. Mice were orally challenged with UPEC strains 536 and CFT073, non-pathogenic strain K12 MG1655, and ΔPAI-536, an isogenic mutant of strain 536 lacking all 7 pathogenicity islands whose virulence is drastically attenuated. Intestinal colonization was measured, and cytokine expression was determined in various organs recovered from mice after oral challenge. UPEC strain 536 efficiently colonized the mouse digestive tract, and prior Enterobacteriaceae colonization was found to impact strain 536 colonization efficiency. An innate immune response, detected as the production of TNFα, IL-6 and IL-10 cytokines, was activated in the ileum 48 hours after oral challenge with strain 536, and returned to baseline within 8 days, without a drop in fecal pathogen load. Although inflammation was detected in the ileum, histology was normal at the time of cytokine peak. Comparison of cytokine secretion 48h after oral gavage with E. coli strain 536, CFT073, MG1655 or ΔPAI-536 showed that inflammation was more pronounced with UPECs than with non-pathogenic or attenuated strains. Pathogenicity islands also seemed to be involved in host detection, as IL-6 intestinal secretion was increased after administration of E. coli strain 536, but not after administration of ΔPAI-536. In conclusion, UPEC colonization of the mouse digestive tract activates acute phase inflammatory cytokine secretion but does not trigger any pathological changes, illustrating the opportunistic nature of UPECs. This digestive tract colonization model will be useful for studying the factors controlling the switch from commensalism to pathogenicity.
IAME, UMR 1137, INSERM, Paris, France.|Univ. Paris Diderot, Sorbonne Paris Cité, Paris, France.|AP-HP, Groupe Hospitalier Universitaire Pitié Salpêtrière Charles Foix, Département d'urologie, néphrologie et transplantation, Paris, France.|Univ. Pierre et Marie Curie, Sorbonne Universités, Paris, France.
Jérôme
http://orcid.org/0000-0003-2998-6531
J
Tourret
Michael Smith Laboratories, The University of British Columbia, Vancouver, Canada.|Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
Benjamin P
BP
Willing
Michael Smith Laboratories, The University of British Columbia, Vancouver, Canada.|British Columbia Centre for Disease Control Public Health Laboratory, Vancouver, British Columbia, Canada.
Matthew A
MA
Croxen
IAME, UMR 1137, INSERM, Paris, France.|Univ. Paris Diderot, Sorbonne Paris Cité, Paris, France.|Institut Pasteur, Molecular Biology of Gene in Extremophiles, Department of Microbiology, Paris, France.|AP-HP, Hôpital Louis Mourier, Service de Réanimation Médico-chirurgicale, Colombes, France.
Nicolas
N
Dufour
IAME, UMR 1137, INSERM, Paris, France.|Univ. Paris Diderot, Sorbonne Paris Cité, Paris, France.
Sara
S
Dion
IAME, UMR 1137, INSERM, Paris, France.|Univ. Paris Diderot, Sorbonne Paris Cité, Paris, France.|Lurie Children's Hospital of Chicago Research Center, Department of pediatrics, Northwestern University Feinberg School of Medicine, Chicago, United States of America.
Sarah
S
Wachtel
IAME, UMR 1137, INSERM, Paris, France.|Univ. Paris Diderot, Sorbonne Paris Cité, Paris, France.
Erick
E
Denamur
Michael Smith Laboratories, The University of British Columbia, Vancouver, Canada.
B Brett
BB
Finlay
D000818:Animals; D004755:Enterobacteriaceae / Q000276:immunology; D004756:Enterobacteriaceae Infections / Q000276:immunology / Q000382:microbiology; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate; D016753:Interleukin-10 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014552:Urinary Tract Infections / Q000276:immunology* / Q000382:microbiology; D056689:Uropathogenic Escherichia coli / Q000276:immunology*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10