Influenza A virus infection of intestinal epithelial cells enhances the adhesion ability of Crohn's disease associated Escherichia coli strains.

Marta Aleandri,Massimiliano Marazzato,Ignacio Celestino,Nicolas Barnich,Serena Schippa,Maria Pia Conte,Giovanna Simonetti,Paola Goldoni,Catia Longhi,Mauro Nicoletti,Lucia Nencioni,Simona Panella,Anna Teresa Palamara,Paola Checconi

doi:10.1371/journal.pone.0117005

Abstract

Modifications of intestinal glycoreceptors expression, in particular CEACAM6, typically found in ileal Crohn's disease (CD), favor, among the commensal species of microbiota, the enrichment in Escherichia coli. Removal of protein glycosidic residues by neuraminidase, a sialidase typical of influenza virus, increases adhesion ability of Escherichia coli to Caco-2 intestinal cells. In this study we investigated whether influenza virus infection of human intestinal epithelial cells could influence the adhesiveness of different Escherichia coli strains isolated from CD patients by altering surface glycoreceptors. Influenza virus infection of intestinal cells increased exposure of galactose and mannose residues on the cell surface. In particular, glycoreceptors Thomsen-Friedenreich and CEACAM6 were over-expressed in influenza virus infected cells. In the same experimental conditions, a significant increase in bacterial adhesiveness was observed, independently of their own adhesive ability. The increase was reverted by treatment with anti-TF and anti-CEACAM6 antibodies. Interestingly, influenza virus was able to efficiently replicate in human primary intestinal cells leading to TF exposure. Finally, intestinal infected cells produced high levels of pro-inflammatory cytokines compared to control. Overall these data suggest that influenza virus infection, could constitute an additional risk factor in CD patients.

Highlights

Inflammatory bowel diseases (IBD), including Crohn’s disease (CD), are immune-mediated disorders originating from a breakdown of the normal symbiosis between the mucosal immune responses and the commensal flora [1,2]
We previously demonstrated that treatment of intestinal cells with Clostridium perfringens neuraminidase, an enzyme characterized by sialidase activity that cuts sialic acids (SA) from the Gal residues, caused a significant increase in the adhesive ability of E. coli strains isolated from bioptic samples of CD pediatric patients, and suggested that this event could be linked to over-exposure of receptors, such as TF antigen [17]
Monolayers of Caco-2 cells (48 hrs post plating) were infected with PR8 virus at different multiplicities of infection (MOI) (0.2, 0.4, and 0.8) for 24 hrs and the cells were infected with E. coli adherent/invasive E. coli (AIEC) LF82, E.coli LF82 ΔfimH or E. coli S15 strains for 2 hrs

Summary

Introduction

Inflammatory bowel diseases (IBD), including Crohn’s disease (CD), are immune-mediated disorders originating from a breakdown of the normal symbiosis between the mucosal immune responses and the commensal flora [1,2]. Changes in the mucosal-associated flora may depend on the abnormal interaction between intestinal cells and microbial lectins caused by an altered glycosylation pattern of mucosal proteins, which is widely observed in CD patients [16] These alterations include the increased expression of oncofetal glycans such as the Thomsen-Friedenreich (TF) receptor and an abnormal ileal expression of carcinoembryonic antigenrelated cell adhesion molecule 6 (CEACAM6), both of which are recognized by E. coli adhesins [17,18,19,20,21]. Influenza virus (IV) infection has been shown to induce over-expression of CEACAM6 protein, probably via interaction with NA followed by activation of the Src/Akt signaling pathway in lung epithelial cells [25]

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Results

Conclusion