Pathogenic Role of Associated Adherent‐Invasive Escherichia coli in Crohn's Disease

Abstract

Several lines of evidence suggest that adherent-invasive Escherichia coli (AIEC) strains play an important role in Crohn's disease (CD). The objective of this study was to investigate the pathogenic role of two AIEC strains, LF82 and O83:H1, in CD patients. Organ cultures of colonic biopsies from patients were set up to assess the effects of LF82 and O83:H1 on the expression of CEACAM6, LAMP1, HLA-DR, ICAM1 by immunohistochemistry and of IL-8, IFNʏ, and TNF-α genes by RT-PCR. Moreover, on Caco2 cells, we analyzed the cell cycle, the expression of MGMT and DNMT1 genes, and DNA damage induced by LF82 and O83:H1, by FACS, RT-PCR, and DAPI staining, respectively. Epithelial and lamina propria mononuclear cells (LPMNC) expression of CEACAM6 and LAMP1 were higher in biopsies cultured in the presence of both O83:H1 and LF82 than in biopsies cultured with non-pathogenic E. coli. Both AIEC strains induced increased expression of ICAM-1 on blood vessels and HLA-DR on LPMNC. We observed higher levels of TNF-α, IFN-γ, and IL-8 transcripts in biopsies cultured with both AIEC strains than in those cultured with NP. Both LF82 and O83:H1, block the cell cycle into S phase, inducing DNA damage, and modulate the expression of DNMT1 and MGMT genes. Our data suggest that LF82 and 083:H1 strains of E. coli are able to increase in CD colonic biopsies the expression of all the pro-inflammatory cytokines and all the mucosal immune markers investigated. J. Cell. Physiol. 232: 2860-2868, 2017. © 2016 Wiley Periodicals, Inc.

Adherent-invasive Escherichia coli in inflammatory bowel disease

“…LF82 and 083:H1 strains induce increased expression of TNF-α, IFN-γ and IL-8 transcripts on colon biopsies of patients with CD and affect cell cycle distribution on Caco2 cell lines 96. AIEC-infected MDM from patients with quiescent CD release significantly higher amounts of IL-6 and TNF-α than those with active disease or from HC 123 124.…”

“…CEACAM6 host receptors are overexpressed at the apical surface of IEC in patients with CD, thus enhancing the colonisation of ileal mucosa by AIEC 90 95. Additionally, LF82 and 083:H1 strains are able to increase CEACAM6 and LAMP1 expression on the surface of IECs, and increase HLA-DR and ICAM1 expression in the lamina propria 96. Some factors expressed by IEC, such as the protective protease meprin, impair AIEC binding to mannosylated host receptors by degrading type 1 fimbriae in a dose-dependent manner, thus protecting ileal mucosa 97.…”

Effects of treatment with Maraviroc a CCR5 inhibitor on a human hepatic stellate cell line

“…The expression of glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) was used for normalization of gene expression values. Melting curve analysis was always performed at the end of each PCR assay to control primer specificity (Esposito et al, ; Mazzarella et al, ; Poletto et al, ). Relative fold change was calculated by 2 −ΔΔCt method.…”

Adherent‐invasive Escherichia coli (AIEC): Cause or consequence of inflammation, dysbiosis, and rupture of cellular joints in patients with IBD?

“…People with CD have an overexpression of CEACAM6 (Barnich et al, 2007) and this is probably due to the increased release of interferon-γ (IFN-γ) and TNF-α in the circulation (Fahlgren et al, 2003). Studies have also shown that the LF82 and 083: H1 strains are able to increase the expression of CEACAM6 and LAMP1 on the IEC surface, as well as the expression of HLA-DR and ICAM1 in the lamina propria (Mazzarella et al, 2017); furthermore, in CEACAM6 transgenic mice, the LF82 strain is able to increase colon hypersensitivity and P2X receptor expression, involved in the transmission of visceral intestinal pain to the colonic hypersensitivity (CHS) (Lashermes et al, 2018). Yersiniabactin iut…”

“…LF82 strain could induce the release of exosomes, which activate NF‐κB, mitogen‐activated protein kinases p38 and c‐Jun N‐terminal kinase, as well as increase the secretion of proinflammatory cytokines in vitro and in vivo. LF82 and 083:H1 strains induce increased expression of TNF‐α, IFN‐γ, and IL‐8 transcripts on colon biopsies of patients with CD and affect cell cycle distribution on Caco2 cell lines (Mazzarella et al, ). LF82 bacteria were unable to activate caspase‐1 and induce IL‐18 production (Jarry et al, ).…”