Crohn disease–associated adherent-invasive E. coli bacteria target mouse and human Peyer’s patches via long polar fimbriae
Benoit Chassaing, Nathalie Rolhion, Amélie de Vallée, Sa’ad Y. Salim, Maelle Prorok-Hamon, Christel Neut, Barry J. Campbell, Johan D. Söderholm, Jean-Pierre Hugot, Jean-Frédéric Colombel, Arlette Darfeuille-Michaud
Benoit Chassaing, Nathalie Rolhion, Amélie de Vallée, Sa’ad Y. Salim, Maelle Prorok-Hamon, Christel Neut, Barry J. Campbell, Johan D. Söderholm, Jean-Pierre Hugot, Jean-Frédéric Colombel, Arlette Darfeuille-Michaud
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Research Article

Crohn disease–associated adherent-invasive E. coli bacteria target mouse and human Peyer’s patches via long polar fimbriae

Abstract

Crohn disease (CD) is a multifactorial disease in which an abnormal immune response in the gastrointestinal (GI) tract leads to chronic inflammation. The small intestine, particularly the ileum, of patients with CD is colonized by adherent-invasive E. coli (AIEC) — a pathogenic group of E. coli able to adhere to and invade intestinal epithelial cells. As the earliest inflammatory lesions are microscopic erosions of the epithelium lining the Peyer’s patches (PPs), we investigated the ability of AIEC bacteria to interact with PPs and the virulence factors involved. We found that AIEC bacteria could interact with mouse and human PPs via long polar fimbriae (LPF). An LPF-negative AIEC mutant was highly impaired in its ability to interact with mouse and human PPs and to translocate across monolayers of M cells, specialized epithelial cells at the surface of PPs. The prevalence of AIEC strains harboring the lpf operon was markedly higher in CD patients compared with controls. In addition, increased numbers of AIEC, but not LPF-deficient AIEC, bacteria were found interacting with PPs from Nod2–/– mice compared with WT mice. In conclusion, we have identified LPF as a key factor for AIEC to target PPs. This could be the missing link between AIEC colonization and the presence of early lesions in the PPs of CD patients.

Authors

Benoit Chassaing, Nathalie Rolhion, Amélie de Vallée, Sa’ad Y. Salim, Maelle Prorok-Hamon, Christel Neut, Barry J. Campbell, Johan D. Söderholm, Jean-Pierre Hugot, Jean-Frédéric Colombel, Arlette Darfeuille-Michaud

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Figure 3

LPF are involved in the ability of AIEC strain LF82 to target M cells.

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LPF are involved in the ability of AIEC strain LF82 to target M cells. I...
Interaction of AIEC bacteria LF82 (A and B) and LF82-ΔlpfA isogenic mutant (C) with Caco-2-cl1 (A) or M-like cell (B and C) monolayers in the presence of 0.5% methyl α-d-mannopyranoside. Phalloidin-TRITC labeling of F-actin (red), anti-O83 antibody labeling of LF82 bacteria (green), and Hoechst labeling of DNA (blue) were used. Confocal photomicrographs of interaction of bacteria with in vitro M cells are representative of 3 separate experiments. Scale bars: 25 μm. (D) Translocation across Caco-2-cl1 or M-like cell monolayers. Results are expressed as CFU of translocated bacteria. Each value is the mean ± SEM of at least 5 separate experiments. (E) Translocation of LF82 bacteria and LF82-ΔlpfA isogenic mutant across M-like cell monolayers after 4 hours infection. Results are expressed as translocated bacteria relative to those obtained for strain LF82, taken as 1. (F) Confocal analysis of murine PP sections after labeling of AIEC LF82 with LPS O83 antibody (green), of M cell with UEA-1 TRITC (red), and DNA with Hoechst (blue). Scale bars: 20 μm. Arrowheads indicate UEA-1–positive cells. (G) Quantification of murine M cell–associated bacteria by confocal microscopy analysis. Bars represent the mean. **P < 0.01, ***P < 0.001.