The T3SS main elements are known. For example, EscN is an ATPase that provides energy to form the complex and enable protein secretion [7] and EspA forms a hollow MG132 filament that constitutes the ‘needle’ of the injectisome, through which the proteins are translocated [8]. One of the proteins injected by T3SS is Tir. This factor

is directed into the host cell membrane and binds intimin [9, 10]. The Tir–intimin union mediates intimate adherence, which is a prolonged contact between the host cell plasma membrane and the bacterial outer membrane, and finally triggers the reorganization of the cytoskeleton. The pathological outcomes of EPEC infection include altered transport of water and electrolytes, disruption of the intestinal barrier, and inflammation [11, 12]. Histological analyses of biopsies from patients and experimentally infected animals have shown that EPEC causes a moderate inflammation characterized by mild mucosal damage, modest oedema

and limited infiltration by phagocytes [2, 13–16]. Mucosal inflammatory response click here to EPEC is low [17] if compared with the effects caused by enteroinvasive pathogens (Salmonella [18] and Shigella [19–21]) and extracellular virulent bacteria (enterohemorragic E. coli [22] and enteroaggregative E. coli [15]) with pronounced inflammation. Therefore, the inflammation provoked by EPEC is conventionally described as moderate [17]. The attenuated host response to EPEC is intriguing given that severe epithelial barrier dysfunction is generally associated with inflammation [23]. It is known that EPEC flagellin

(FliC) activates the secretion of interleukin 8 (IL-8) [24] produced by the activation of several signalling pathways [25]. Toll-like receptor 5 (TLR5) is the host molecule that recognizes FliC and activates the immune response [26]. Accordingly, EPEC infection triggers nuclear factor of the kappa B (NF-κB) and extracellular-regulated kinases 1 and 2 (ERK1/2) signalling [27, 28], although some reports indicate that EPEC could modulate the activation [29]. When active, ERK1/2 and NF-κB regulate transcription of genes involved in inflammation [30, 31]. IL-8 is a chemokine produced by EPEC-infected cells. However, Fenbendazole blocking IL-8 only partially decreases chemotaxis of polymorphonuclear cells [32]. Most of the knowledge on the cell response to EPEC infection results from observations obtained separately. Research has generally been done with only one EPEC strain (E2348/69), which halts the knowledge about other strains. The use of different cell lines makes it difficult to establish a general model for the epithelial response, and the studies focused only on the secretion of IL-8 that resulted in an incomplete analysis of other cytokines.