title: Transient Cannabinoid Receptor 2 Blockade during Immunization Heightens Intensity and Breadth of Antigen-specific Antibody Responses in Young and Aged mice.
abstract: The hallmark of vaccines is their ability to prevent the spread of infectious pathogens and thereby serve as invaluable public health tool. Despite their medical relevance, there is a gap in our understanding of the physiological factors that mediate innate and adaptive immune response to vaccines. The endocannabinoid (eCB) system is a critical modulator of homeostasis in vertebrates. Our results indicate that macrophages and dendritic cells produce the endocannabinoid, 2-arachidonoyl-sn-glycerol (2-AG) upon antigen activation. We have also established that 2-AG levels are upregulated in the serum and in the lymph node of mice during vaccination. We hypothesized that the intrinsic release of eCBs from immune cells during activation by pathogenic antigens mitigate inflammation, but also suppress overall innate and adaptive immune response. Here we demonstrate, for the first time, that transient administration of the cannabinoid receptor 2 antagonist AM630 (10 mg/kg) or inverse agonist JTE907 (3 mg/kg) during immunization heightens the intensity and breadth of antigen-specific immune responses in young and aged mice through the upregulation of immunomodulatory genes in secondary lymphoid tissues.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California Irvine, Irvine, CA, USA.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Dotsey
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California Irvine, Irvine, CA, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Ushach
authors.affiliation: Department of Pharmaceutical Sciences, University of California Irvine, Irvine, CA, USA.
authors.forename: Egest
authors.initials: E
authors.lastname: Pone
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California Irvine, Irvine, CA, USA.
authors.forename: Rie
authors.initials: R
authors.lastname: Nakajima
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California Irvine, Irvine, CA, USA.
authors.forename: Algis
authors.initials: A
authors.lastname: Jasinskas
authors.affiliation: Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, CA, USA.
authors.forename: Donovan A
authors.initials: DA
authors.lastname: Argueta
authors.affiliation: Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, CA, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Dillon
authors.affiliation: Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, CA, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: DiPatrizio
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California Irvine, Irvine, CA, USA.
authors.forename: Huw
authors.initials: H
authors.lastname: Davies
authors.affiliation: Department of Physiology &Biophysics, University of California Irvine, Irvine CA, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Zlotnik
authors.affiliation: Malaria Infection Biology and Immunity Unit, Laboratory of Immunogenetics, NIAID, NIH, Rockville, MD, USA.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Crompton
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California Irvine, Irvine, CA, USA.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Felgner
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism; D002186:Cannabinoids / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D063388:Endocannabinoids / Q000378:metabolism; D005260:Female; D005989:Glycerides / Q000378:metabolism; D007114:Immunization; D056747:Immunomodulation / Q000235:genetics; D016130:Immunophenotyping; D007211:Indoles / Q000494:pharmacology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D005989:Glycerides; D007211:Indoles; D043885:Receptor, Cannabinoid, CB2; C094503:glyceryl 2-arachidonate; C094023:iodopravadoline