Chapter 11 - Toxin-Based Modulators for Regulation of Mucosal Immune Responses

Abstract

Exposure of mucosal surfaces to pathogen-associated molecular patterns (PAMPs) from bacterial or viral pathogens stimulates a cascade of innate immune signals that ultimately lead to the development of specific immune responses both at the site of microbial infection and in the general bloodstream. Unlike pathogens, protein and carbohydrate antigens are devoid of PAMPs, and their recognition by host cells does not lead to activation of danger-associated molecular patterns. In fact, mucosal exposure to antigens generally results in the induction of tolerance or mucosal tolerance. Thus the development of subunit vaccines consisting of protein or carbohydrate antigens to be delivered via mucosal routes requires identification and incorporation of adjuvants capable of preventing the development of tolerance and promoting generalized immunity in mucosal tissues and the bloodstream. The bacterial enterotoxin cholera toxin was the first adjuvant reported to induce generalized mucosal and systemic immunity against orally coadministered vaccine antigens. Other toxins and toxin derivatives have now been described to be effective mucosal adjuvants. We will summarize the current knowledge about the mechanisms employed by these toxins and derivatives to promote mucosal immunity. We will also discuss the versatility of toxin-based modulation of immune responses at mucosal sites and their use for induction of tolerance.