The Inflammatory Response during Enterohemorrhagic Escherichia coli Infection

Abstract

The inflammatory response is an integral part of host defense against enterohemorrhagic Escherichia coli (EHEC) infection and also contributes to disease pathology. In this article we explore the factors leading to inflammation during EHEC infection and the mechanisms EHEC and other attaching and effacing (A/E) pathogens have evolved to suppress inflammatory signaling. EHEC stimulates an inflammatory response in the intestine through host recognition of bacterial components such as flagellin and lipopolysaccharide. In addition, the activity of Shiga toxin and some type III secretion system effectors leads to increased tissue inflammation. Various infection models of EHEC and other A/E pathogens have revealed many of the immune factors that mediate this response. In particular, the outcome of infection is greatly influenced by the ability of an infected epithelial cell to mount an effective host inflammatory response. The inflammatory response of infected enterocytes is counterbalanced by the activity of type III secretion system effectors such as NleE and NleC that modify and inhibit components of the signaling pathways that lead to proinflammatory cytokine production. Overall, A/E pathogens have taught us that innate mucosal immune responses in the gastrointestinal tract during infection with A/E pathogens are highly complex and ultimate clearance of the pathogen depends on multiple factors, including inflammatory mediators, bacterial burden, and the function and integrity of resident intestinal epithelial cells.

EspFu-Mediated Actin Assembly Enhances Enteropathogenic Escherichia coli Adherence and Activates Host Cell Inflammatory Signaling Pathways

“…EPEC also encodes a vast repertoire of non-LEE-encoded effectors that are not directly involved with cytoskeleton remodeling but instead play an important role in the modulation of host inflammatory response during the course of infection (20)(21)(22)(23)(24)(25)(26)(27). These effectors are highly conserved among AE pathogens and are generally encoded by genomic islands, suggesting that the acquisition of these elements was necessary to attenuate the inflammatory response triggered by EPEC's interaction with the host cell.…”

Programmed Cell Death in the Evolutionary Race against Bacterial Virulence Factors

“…There is mounting evidence that EPEC inhibits the transcriptional responses of the IEC to which it is attached, effectively shutting down the TNF signaling pathway (Pearson and Hartland 2014). EPEC attacks TAB2 and TAB3, which are adaptors for TAK1 downstream from RIPK1.…”

Overview and Historical Perspectives

“…Tarr and coauthors review in chapter 15 (58) the clinical features of STEC infections in humans, including outcomes and prognosis, and provide insights from both gastroenterological and nephrological perspectives. The inflammatory response to STEC infection and the virulence factors these pathogens have evolved to thwart this response are discussed by Pearson and Hartland in chapter 16 (85). Unfortunately, no ideal therapy is available for STEC infections, and the use of antimicrobials is contraindicated, at least for typical EHEC infections, although investigators of the German O104:H4 outbreak reported the benefit of azithromycin treatment to reduce fecal shedding of the organism.…”