title: Enhancement of humoral immunity by the type II heat-labile enterotoxin LT-IIb is dependent upon IL-6 and neutrophils.
abstract: LT-IIb, a type II heat-labile enterotoxin produced by Escherichia coli, is a potent intradermal adjuvant that enhances immune responses to coadministered antigens. Although the immune mechanisms that promote this augmented immune response have not been well defined, prior intradermal immunization experiments suggested that early cellular and immunomodulatory events at the site of immunization modulated the augmentation of antigen-specific immune responses by LT-IIb. To investigate that hypothesis, mice were intradermally immunized with a recombinant ricin vaccine, a prospective toxin subunit antigen, in the presence and absence of LT-IIb. Analysis of tissue-fluid collection, coupled with histologic sections from the site of intradermal immunization, revealed that a single dose of LT-IIb induced local production of interleukin 6 and promoted a regional infiltration of neutrophils. The adjuvant effects of LT-IIb were abrogated in interleukin 6-deficient mice and when mice were depleted of neutrophils by pretreatment with anti-Ly6G. Overall, these data firmly demonstrated that LT-IIb, when used as an intradermal adjuvant, recruits neutrophils and is a potent rapid inducer of interleukin 6.
authors.affiliation: Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA; Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA;
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Greene
authors.affiliation: Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA; Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA;
authors.forename: John C
authors.initials: JC
authors.lastname: Hu
authors.affiliation: Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York, USA; and.
authors.forename: David J
authors.initials: DJ
authors.lastname: Vance
authors.affiliation: Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York, USA; and.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Rong
authors.affiliation: Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA; Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA;
authors.forename: Lorrie
authors.initials: L
authors.lastname: Mandell
authors.affiliation: Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA; Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA;
authors.forename: Natalie
authors.initials: N
authors.lastname: King-Lyons
authors.affiliation: Department of Biotechnical and Clinical Laboratory Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA;
authors.forename: Patricia
authors.initials: P
authors.lastname: Masso-Welch
authors.affiliation: Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York, USA; and Department of Biomedical Sciences, University at Albany, Albany, New York nicholas.mantis@health.ny.gov.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Mantis
authors.affiliation: Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA; Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA; connell@buffalo.edu.
authors.forename: Terry D
authors.initials: TD
authors.lastname: Connell
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000494:pharmacology; D004768:Enterotoxins / Q000008:administration & dosage* / Q000494:pharmacology; D029968:Escherichia coli Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D056724:Immunity, Humoral / Q000187:drug effects / Q000276:immunology*; D007114:Immunization; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D015850:Interleukin-6 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D012871:Skin Diseases / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D014612:Vaccines / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D015850:Interleukin-6; C509236:RiVax; D014612:Vaccines; C577686:interleukin-6, mouse; C027538:heat-labile enterotoxin, E coli
keywords: Lys6G; adjuvant; interleukin-6; intradermal; vaccine