Fig. 1.

Complexity of the host response to Clostridium difficile infection (CDI). (A) Intoxication of host epithelial cells by C. difficile toxins produced by vegetative cells is primary to inflammatory response. Toxin production and secretion increases after vegetative cells enter into the stationary growth phase [22,39]. During cell infection, the toxins are subjects to time-dependent degradation due to proteolysis and pH effects. The toxin’s entry into the intestinal epithelial cells is one of the earliest pathogenic events. It leads to loss of structural integrity (actin skeleton disruption, disruption of tight junctions, reduced cell–cell contact), cell death and epithelium disruption. TLR, Toll-like receptor. (B) Inflammatory response by two mechanisms: (i) secondary to toxin intoxication (within a few hours after toxin exposure); and (ii) activation of intracellular cascades by non-toxin virulence factors such as surface layer proteins (SLPs), flagellar proteins (FliC and FliD), adhesins (cwp66, cwpV), fibronectin-binding proteins and cell surface polysaccharides [22]. (C) CDI clinical manifestation. The inflammatory response causes tissue damage: neutrophil accumulation (one of the major mechanisms) is responsible for pseudomembrane formation seen in severe colitis [38]; diarrhoea, toxic megacolon. Toxin B can also cause multiple organ dysfunction syndrome due to systemic toxin damage [50,68].