Abstract
Cholera toxin B subunit (CTB) is a mucosal immunomodulatory protein that induces robust mucosal and systemic antibody responses. This well-known biological activity has been exploited in cholera prevention (as a component of Dukoral® vaccine) and vaccine development for decades. On the other hand, several studies have investigated CTB’s immunotherapeutic potential in the treatment of inflammatory diseases such as Crohn’s disease and asthma. Furthermore, we recently found that a variant of CTB could induce colon epithelial wound healing in mouse colitis models. This review summarizes the possible mechanisms behind CTB’s anti-inflammatory activity and discuss how the protein could impact mucosal inflammatory disease treatment.
Highlights
Vibrio cholerae is a gram-negative bacterium that can colonize the gastrointestinal tract and cause life-threatening watery diarrhea
The detailed mechanism by which recombinant CTB (rCTB) inhibited Th1 cell was not elucidated, it is possible that the binding of Cholera toxin B subunit (CTB) to GM1 ganglioside on immune cells resulted in a signaling cascade of events that led to Th1 inhibition, because non-GM1 binding CTB mutants do not modulate lymphocyte function [48]
Showed that the binding of rCTB to GM1 ganglioside directly prevented the activation and proliferation of CD4+ T cells [50]. This effect was induced by rCTB-mediated sphingomyelinase activation that subsequently increased the production of ceramides, which are known cell cycle arrest inducers [51]. rCTB inhibited protein kinase Cα, a pro-growth cellular regulator, which was linked to rCTB-induced lipid raft modifications and ceramide-mediated inactivation [52,53]
Summary
Vibrio cholerae is a gram-negative bacterium that can colonize the gastrointestinal tract and cause life-threatening watery diarrhea. It has been previously shown that CTB can induce strong biological activities that can enhance or suppress immune effects under normal and various immunopathological conditions without the toxicity associated with the CTA subunit [4]. In its most well-known immunostimulatory effects, CTB is used in the vaccine Dukoral®. The presence of GM1 ganglioside on the luminal surface of intestinal epithelial cells and antigen presenting cells (APCs) in the gut seems to be essential for CTB’s strong mucosal immunostimulatory effects associated with MHC class II expression and local antigen enrichment [13]. The underlying mechanisms are not well understood, recent studies have shed some light on these immunosuppressive effects induced by CTB. This review will summarize published studies on CTB’s impacts in mucosal inflammatory disease models, as well as the mechanisms associated with its therapeutic effect and the challenges that CTB faces as an immunomodulatory drug
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