title: Dendritic Cell-Mediated Mechanisms Triggered by LT-IIa-B5, a Mucosal Adjuvant Derived from a Type II Heat-Labile Enterotoxin ofEscherichia coli.
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 ofEscherichia coliheat-labile enterotoxin type IIa (LT-IIa-B5), a potent non-toxic mucosal adjuvant. Alternations in gene expression in response to LT-IIa-B5were 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-B5enhanced 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-B5serve as a critical mechanism whereby this potent adjuvant amplifies mucosal immunity to co-administered antigens.
authors.affiliation: Bio & Drug Discovery Division, Center for Drug Discovery Technology, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea.|Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34114, Republic of Korea.
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Microbiology, School of Dental Medicine, The University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: George
authors.initials: G
authors.lastname: Hajishengallis
authors.affiliation: 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, Buffalo, NY 14214, USA.
authors.forename: Terry D
authors.initials: TD
authors.lastname: Connell
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D019013:CD40 Antigens / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018121:Receptors, Cytokine / Q000096:biosynthesis
chemical_list: D000276:Adjuvants, Immunologic; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D001427:Bacterial Toxins; D019013:CD40 Antigens; D018925:Chemokines; D016207:Cytokines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D018121:Receptors, Cytokine; C027538:heat-labile enterotoxin, E coli
keywords: LT-IIa-B5; dendritic cells; immune cell migration; lymph node; mucosal vaccine adjuvant