title: The mucosal adjuvant cyclic di-AMP exerts immune stimulatory effects on dendritic cells and macrophages.
abstract: The cyclic di-nucleotide bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di-AMP) is a candidate mucosal adjuvant with proven efficacy in preclinical models. It was shown to promote specific humoral and cellular immune responses following mucosal administration. To date, there is only fragmentary knowledge on the cellular and molecular mode of action of c-di-AMP. Here, we report on the identification of dendritic cells and macrophages as target cells of c-di-AMP. We show that c-di-AMP induces the cell surface up-regulation of T cell co-stimulatory molecules as well as the production of interferon-β. Those responses were characterized by in vitro experiments with murine and human immune cells and in vivo studies in mice. Analyses of dendritic cell subsets revealed conventional dendritic cells as principal responders to stimulation by c-di-AMP. We discuss the impact of the reported antigen presenting cell activation on the previously observed adjuvant effects of c-di-AMP in mouse immunization studies.
authors.affiliation: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Ivana
authors.initials: I
authors.lastname: Škrnjug
authors.affiliation: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Rueckert
authors.affiliation: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Rimma
authors.initials: R
authors.lastname: Libanova
authors.affiliation: Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lienenklaus
authors.affiliation: Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weiss
authors.affiliation: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Guzmán
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009092:Mucous Membrane / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D061025:Costimulatory and Inhibitory T-Cell Receptors; D015226:Dinucleoside Phosphates; C528998:cyclic diadenosine phosphate; D016899:Interferon-beta
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