Host Immune Responses to Clostridioides difficile: Toxins and Beyond

Abstract

Clostridioides difficile is often resistant to the actions of antibiotics to treat other bacterial infections and the resulting C. difficile infection (CDI) is among the leading causes of nosocomial infectious diarrhea worldwide. The primary virulence mechanism contributing to CDI is the production of toxins. Treatment failures and recurrence of CDI have urged the medical community to search for novel treatment options. Strains that do not produce toxins, so called non-toxigenic C. difficile, have been known to colonize the colon and protect the host against CDI. In this review, a comprehensive description and comparison of the immune responses to toxigenic C. difficile and non-toxigenic adherence, and colonization factors, here called non-toxin proteins, is provided. This revealed a number of similarities between the host immune responses to toxigenic C. difficile and non-toxin proteins, such as the influx of granulocytes and the type of T-cell response. Differences may reflect genuine variation between the responses to toxigenic or non-toxigenic C. difficile or gaps in the current knowledge with respect to the immune response toward non-toxigenic C. difficile. Toxin-based and non-toxin-based immunization studies have been evaluated to further explore the role of B cells and reveal that plasma cells are important in protection against CDI. Since the success of toxin-based interventions in humans to date is limited, it is vital that future research will focus on the immune responses to non-toxin proteins and in particular non-toxigenic strains.

Curcumin and capsaicin regulate apoptosis and alleviate intestinal inflammation induced by Clostridioides difficile in vitro

“…According to a previous study, proteomic analysis of C. difficile revealed that several other virulence factors such as extracellular proteases, surface layer proteins (SLP) A, cell wall-binding protein (CWP), collagen-binding protein (CbpA), fibronectin-binding protein (FBP) type IV pili and flagella can also contribute to disease severity and host colonization [80][81][82][83]. These bacterial factors possess potent pro-inflammatory activities, and are capable of causing intestinal mucosal injury by promoting inflammatory responses [80,[84][85][86]. For instance, recognition of C. difficile flagellin by toll-like receptor 5 (TLR-5) results in activation of NF-κB and MAPKs pathways, which in turn can induce the production of additional growth factors and cytokines [87].…”

An Update on Clostridioides difficile Binary Toxin

“…Little is known about CDT and its role in immune response; however, CDT may enhance the disruption of the host’s protective mechanisms stimulated by C. difficile toxins A and B [ 28 ]. It has been shown that CDT enhances the virulence of RT027 strains in animal models by inducing pathogenic host inflammation, resulting in eosinophil apoptosis in the colon and blood [ 29 ].…”

Immunological mechanisms of fecal microbiota transplantation in recurrent Clostridioides difficile infection

“…As there are recent and excellent reviews on the immune response to C. difficile [ 10 , 42 , 43 ], in this section, we present the main characteristics of this host-pathogen interaction.…”