Abstract

Mucosal tissues are the initial site through which most pathogens invade. As such, vaccines and adjuvants that modulate mucosal immune functions have emerged as important agents for disease prevention. Herein, we investigated the immunomodulatory mechanisms of the B subunit of Escherichia coli heat-labile enterotoxin type IIa (LT-IIa-B5), a potent non-toxic mucosal adjuvant. Alternations in gene expression in response to LT-IIa-B5 were identified using a genome-wide transcriptional microarray that focused on dendritic cells (DC), a type of cell that broadly orchestrates adaptive and innate immune responses. We found that LT-IIa-B5 enhanced the homing capacity of DC into the lymph nodes and selectively regulated transcription of pro-inflammatory cytokines, chemokines, and cytokine receptors. These data are consistent with a model in which directional activation and differentiation of immune cells by LT-IIa-B5 serve as a critical mechanism whereby this potent adjuvant amplifies mucosal immunity to co-administered antigens.

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