title: Neutrophils negatively regulate induction of mucosal IgA responses after sublingual immunization.
abstract: Induction of mucosal immunoglobulin-A (IgA) capable of providing a first line of defense against bacterial and viral pathogens remains a major goal of needle-free vaccines given via mucosal routes. Innate immune cells are known to play a central role in induction of IgA responses by mucosal vaccines, but the relative contribution of myeloid cell subsets to these responses has not firmly been established. Using an in vivo model of sublingual vaccination with Bacillus anthracis edema toxin (EdTx) as adjuvant, we examined the role of myeloid cell subsets for mucosal secretory IgA responses. Sublingual immunization of wild-type mice resulted in a transient increase of neutrophils in sublingual tissues and cervical lymph nodes. These mice later developed Ag-specific serum IgG responses, but not serum or mucosal IgA. Interestingly, EdTx failed to increase neutrophils in sublingual tissues and cervical lymph nodes of IKKβ(ΔMye) mice, and these mice developed IgA responses. Partial depletion of neutrophils before immunization of wild-type mice allowed the development of both mucosal and serum IgA responses. Finally, co-culture of B cells with neutrophils from either wild-type or IKKβ(ΔMye) mice suppressed secretion of IgA, but not IgM or IgG. These results identify a new role for neutrophils as negative regulators of IgA responses.
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA.
authors.forename: J
authors.initials: J
authors.lastname: Jee
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA.
authors.forename: A
authors.initials: A
authors.lastname: Bonnegarde-Bernard
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA.
authors.forename: A
authors.initials: A
authors.lastname: Duverger
authors.affiliation: Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA.
authors.forename: E
authors.initials: E
authors.lastname: Cormet-Boyaka
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Martin
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA.
authors.forename: H E
authors.initials: HE
authors.lastname: Steiner
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Bachman
authors.affiliation: 1] Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA [2] Internal Medicine, The Ohio State University, Columbus, Ohio, USA [3] Center for Microbial Interface Biology, The Ohio State University, Columbus, Ohio, USA.
authors.forename: P N
authors.initials: PN
authors.lastname: Boyaka
mesh_terms: D000286:Administration, Sublingual; D000818:Animals; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001427:Bacterial Toxins / Q000276:immunology; D051550:I-kappa B Kinase / Q000172:deficiency / Q000378:metabolism; D018928:Immunity, Mucosal; D007114:Immunization; D007071:Immunoglobulin A, Secretory / Q000276:immunology*; D007958:Leukocyte Count; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000276:immunology* / Q000378:metabolism; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D007071:Immunoglobulin A, Secretory; C030325:anthrax toxin; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse