Heat-Labile Enterotoxins as Adjuvants or Anti-Inflammatory Agents

Abstract

Escherichia coli and Vibrio cholerae produce structurally related AB₅-type heat-labile enterotoxins, which are classified into two major types. The Type I subfamily includes cholera toxin and E. coli LT-I, whereas the Type II subfamily comprises LT-IIa and LT‐IIb. In addition to their roles in microbial pathogenesis, the enterotoxins are widely and intensively studied for their exceptionally strong adjuvant and immunomodulatory activities, which are not necessarily dependent upon their abilities to elevate intracellular cAMP levels. Despite general structural similarities, these molecules, in intact or derivative form, display notable differences in their interactions with gangliosides or Toll-like receptors. This divergence results in differential immune response outcomes, the underlying mechanisms of which remain largely uncharacterized. Whereas the study of these molecules has been pivotal in understanding basic mechanisms of immune regulation, a formidable challenge is to dissociate toxicity from useful properties that can be exploited in vaccine development or for the treatment of autoimmune inflammatory diseases.

Keywords:

• heat-labile enterotoxins
• adjuvants
• vaccines
• gangliosides
• toll-like receptors
• inflammation

ACKNOWLEDGMENTS

Studies performed in the authors' lab and cited in this review were supported by U.S. Public Health Service Grants DE015254 and DE017138 to GH.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.