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Dendritic Cell-Mediated Mechanisms Triggered by LT-IIa-B5, a Mucosal Adjuvant Derived from a Type II Heat-Labile Enterotoxin of Escherichia coli

  • Lee, Chang Hoon (Bio & Drug Discovery Division, Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology (KRICT)) ;
  • Hajishengallis, George (Department of Microbiology, School of Dental Medicine, The University of Pennsylvania) ;
  • Connell, Terry D. (Department of Microbiology & Immunology and The Witebsky Center for Microbial Pathogenesis and Immunology, The Jacob's School of Medicine and Biomedical Sciences, The University at Buffalo, State University of New York)
  • Received : 2016.11.29
  • Accepted : 2017.01.31
  • Published : 2017.04.28

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 ($LT-IIa-B_5$), a potent non-toxic mucosal adjuvant. Alternations in gene expression in response to $LT-IIa-B_5$ 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 $LT-IIa-B_5$ 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 $LT-IIa-B_5$ serve as a critical mechanism whereby this potent adjuvant amplifies mucosal immunity to co-administered antigens.

Keywords

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