Epithelial cell signaling responses to enterohemorrhagic Escherichia coli infection (original) (raw)
Related papers
The role of epithelial malfunction in the pathogenesis of enteropathogenic E. coli-induced diarrhea
Laboratory Investigation, 2009
The homeostatic balance of the gastrointestinal tract relies on a single layer of epithelial cells, which assumes both digestive and protective functions. Enteric pathogens, including enteropathogenic Escherichia coli (EPEC), have evolved numerous mechanisms to disrupt basic intestinal epithelial functions, promoting the development of gastrointestinal disorders. Despite its non-invasive nature, EPEC inflicts severe damage to the intestinal mucosa, including the dysregulation of water and solute transport and the disruption of epithelial barrier structure and function. Despite the high prevalence and morbidity of disease caused by EPEC infections, the etiology of its pathogenesis remains incompletely understood. This review integrates the newest findings on EPEC-epithelial interactions with established mechanisms of disease in an attempt to give a comprehensive understanding of the cellular processes whereby this common pathogen may cause diarrheal illness.
Infection and Immunity, 1998
Enterohemorrhagic Escherichia coli (EHEC) infection is associated with watery diarrhea and can lead to complications, including hemorrhagic colitis and the hemolytic-uremic syndrome. The mechanisms by which these organisms produce diarrheal disease remain to be elucidated. Changes in T84 epithelial cell electrophysiology were examined following EHEC infection. T84 cell monolayers infected with EHEC O157:H7 displayed a time-dependent decrease in transepithelial resistance. Increases in the transepithelial flux of both [ 3 H]mannitol and 51 Cr-EDTA accompanied the EHEC-induced decreases in T84 resistance. Altered barrier function induced by EHEC occurred at the level of the tight junction since immunofluorescent staining of the tight-junction-associated protein ZO-1 was disrupted when examined by confocal microscopy. Decreased resistance induced by EHEC involved a protein kinase C (PKC)-dependent pathway as the highly specific PKC inhibitor, CGP41251, abrogated the EHEC-induced drop i...
Enterohemorrhagic Escherichia coli Pathogenesis and the Host Response
Microbiology Spectrum, 2014
Enterohemorrhagic Escherichia coli (EHEC) is a highly pathogenic bacterial strain capable of causing watery or bloody diarrhea, the latter termed hemorrhagic colitis, and hemolytic-uremic syndrome (HUS). HUS is defined as the simultaneous development of non-immune hemolytic anemia, thrombocytopenia, and acute renal failure. The mechanism by which EHEC bacteria colonize and cause severe colitis, followed by renal failure with activated blood cells, as well as neurological symptoms, involves the interaction of bacterial virulence factors and specific pathogen-associated molecular patterns with host cells as well as the host response. The innate immune host response comprises the release of antimicrobial peptides as well as cytokines and chemokines in addition to activation and/or injury to leukocytes, platelets, and erythrocytes and activation of the complement system. Some of the bacterial interactions with the host may be protective in nature, but, when excessive, contribute to exte...
A new understanding of enteroaggregative Escherichia coli as an inflammatory pathogen
Cell Adhesion & Migration, 2012
E nteroaggregative Escherichia coli (EAEC) is an important cause of endemic and epidemic diarrheal disease worldwide. Although not classically considered an inflammatory pathogen in the style of Shigella and Salmonella species, clinical data from patients suggests that inflammatory responses may play an important role during EAEC disease. However, the specific role of inflammation during EAEC pathogenesis has not been investigated in detail. To better understand how EAEC may induce inflammation, we have focused our attention on the intimate interactions between EAEC and the host epithelium and the subsequent induction of host cell signaling events leading to innate immune responses. Here, we discuss our recent findings on the signaling pathway by which EAEC promotes transepithelial migration of polymorphonuclear leukocytes (PMNs), the role of aggregative adherence fimbriae in triggering this event and the implementation of human intestinal xenografts in immunodeficient mice for studying EAEC pathogenesis in vivo. Our findings suggest that EAEC shares conserved mechanisms of inducing PMN recruitment with other intestinal pathogens, providing new insight into the potential pathological consequences of EAEC-induced inflammation.
Journal of Infectious Diseases, 2012
Background. Enteroaggregative Escherichia coli (EAEC) are increasingly recognized as an important agent of inflammatory and often persistent diarrhea. Although previous studies report on the inflammatory aspects of EAEC pathogenesis, the mechanisms by which EAEC trigger these events are not well understood. Methods. EAEC strains harboring mutations in known EAEC virulence determinants were tested in an in vitro model of transepithelial migration of polymorphonuclear neutrophils (PMNs) and in human intestinal xenografts in severe-combined immunodeficient (SCID-HU-INT) mice, a novel model for studying EAEC disease in vivo. Results. Expression of aggregative adherence fimbriae (AAFs), the principal adhesins of EAEC, was required for EAEC-induced PMN transepithelial migration in vitro. Moreover, constructed plasmids encoding AAF gene clusters demonstrated that the AAF adhesins are sufficient for triggering this event in a nonpathogenic E. coli background. Furthermore, with use of the SCID-HU-INT mouse model, severe tissue damage and infiltration of inflammatory cells was observed in the human tissue after EAEC infection. These pathological marks were strongly related to AAF expression, thus clearly confirming our in vitro findings. Conclusions. The present work establishes EAEC as an important inflammatory pathogen and the AAF adhesins as inducers of potentially detrimental immune responses.
Differentiation, 1995
Pathogens and eucaryotic cells are active partners during the process of pathogenicity. To gain access to enterocytes and to cross the epithelial membrane, many enterovirulent microorganisms interact with the brush border membrane-associated components as receptors. Recent reports provide evidence that intestinal cell differentiation plays a role in microbial pathogenesis. Human enteropathogenic Escherichia coli (EPEC) develop their pathogenicity upon infecting enterocytes. To determine if intestinal epithelial cell differentiation influences EPEC pathogenicity, we examined the infection of human intestinal epithelial cells by JPN 15 (pMAR7) [EAF+ eae+] EPEC strain as a function of the cell differentiation. The human embryonic intestinal INT407 cells, the human colonic T,, cells, the human undifferentiated HT-29 cells (HT-29 Std) and two enterocytic cell lines, HT-29 glc-/+ and Caco-2 cells, were used as cellular models. Cells were infected apically with the EPEC strain and the cell-association and cellentry were examined by quantitative determination using metabolically radiolabeled bacteria, as well as by light, scanning and tranmission electron microscopy. [EAF+ eae+] EPEC bacteria efficiently colonized the cultured human intestinal cells. Diffuse bacterial adhesion occurred to undifferentiated HT-29 Std and INT407 cells, whereas characteristic EPEC cell clusters were observed on fully differentiated enterocytic HT-29 glc-/+ cells and on colonic crypt T,, cells. As shown using the Caco-2 cell line, which spontaneously differentiates in culture, the formation of EPEC clusters increased as a function of the epithelial cell differentiation. In contrast, efficient cell-entry of [EAF+ eae+] EPEC bacteria occured in recently differentiated Caco-2 cells and decreased when the cells were fully differentiated. Our results provide evidence that the intestinal cell differentiation could play a dual role in EPEC pathogenesis: it up-regulates intestinal cell colonization and down-regulates intestinal cell invasion.
The ex vivo response of human intestinal mucosa to enteropathogenic Escherichia coli infection
Cellular Microbiology, 2009
In vitro organ culture (IVOC) represents a gold standard model to study enteropathogenic E. coli (EPEC) infection of human intestinal mucosa. However, the optimal examination of the bacterialhost cell interaction requires a directional epithelial exposure, without serosal or cut surface stimulation. A polarised IVOC system (pIVOC) was developed in order to overcome such limitations: apical EPEC infection produced negligible bacterial leakage via biopsy edges, resulted in enhanced colonisation compared to standard IVOC, and showed evidence of bacterial detachment, as in natural rabbit EPEC infections. Examination of mucosal innate immune responses in pIVOC showed both interleukin (IL)-8 mRNA and protein levels were significantly increased after apical EPEC infection. Increased IL-8 levels mainly depended on flagellin expression as fliC-negative EPEC did not elicit a significant IL-8 response despite increased mucosal colonisation compared to wild type EPEC. In addition, apical application of purified flagella significantly increased IL-8 protein levels over non-infected controls. Immunofluorescence staining of EPEC-infected small intestinal biopsies revealed apical and basolateral distribution of Toll-like receptor (TLR) 5 on epithelium suggesting that EPEC can trigger mucosal IL-8 responses by apical flagellin/TLR5 interaction ex vivo and does not require access to the basolateral membrane as postulated in cell culture models.
A comparison of enteropathogenic and enterohaemorrhagic Escherichia coli pathogenesis
FEMS Microbiology Letters, 2006
This review covers enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC) infections, focusing on differences in their virulence factors and regulation. While Shiga-toxin expression from integrated bacteriophages sets EHEC apart from EPEC, EHEC infections often originate from asymptomatic carriage in ruminants whereas human EPEC are considered to be overt pathogens and more host-restricted. In part, these differences reflect variation in adhesin repertoire, type III-secreted effectors and the way in which these factors are regulated.
Interaction of enterohemorrhagic Escherichia coli O157:H7 with mouse intestinal mucosa
FEMS Microbiology Letters, 2008
In this study, we used mouse ileal loops to investigate the interaction of enterohemorrhagic Escherichia coli (EHEC) O157:H7 with the mouse intestinal mucosa. With a dose of 10 9 and 3 h incubation, EHEC O157 was detected in the lumen and to a lesser extent associated with the epithelium. Typical attaching and effacing (A/E) lesions were seen, albeit infrequently. While the effector protein Tir was essential for A/E lesion formation, the bacterial type III secretion system adaptor protein TccP was dispensable. These results suggest that A/E lesions on mouse intestinal mucosa can be formed independently of robust actin polymerization.