title: Macrophage Death following Influenza Vaccination Initiates the Inflammatory Response that Promotes Dendritic Cell Function in the Draining Lymph Node.
abstract: The mechanism by which inflammation influences the adaptive response to vaccines is not fully understood. Here, we examine the role of lymph node macrophages (LNMs) in the induction of the cytokine storm triggered by inactivated influenza virus vaccine. Following vaccination, LNMs undergo inflammasome-independent necrosis-like death that is reliant on MyD88 and Toll-like receptor 7 (TLR7) expression and releases pre-stored interleukin-1α (IL-1α). Furthermore, activated medullary macrophages produce interferon-β (IFN-β) that induces the autocrine secretion of IL-1α. We also found that macrophage depletion promotes lymph node-resident dendritic cell (LNDC) relocation and affects the capacity of CD11b+LNDCs to capture virus and express co-stimulatory molecules. Inhibition of the IL-1α-induced inflammatory cascade reduced B cell responses, while co-administration of recombinant IL-1α increased the humoral response. Stimulation of the IL-1α inflammatory pathway might therefore represent a strategy to enhance antigen presentation by LNDCs and improve the humoral response against influenza vaccines.
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, via Vincenzo Vela 6, 6500 Bellinzona, Switzerland.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Chatziandreou
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, via Vincenzo Vela 6, 6500 Bellinzona, Switzerland.
authors.forename: Yagmur
authors.initials: Y
authors.lastname: Farsakoglu
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, via Vincenzo Vela 6, 6500 Bellinzona, Switzerland.
authors.forename: Miguel
authors.initials: M
authors.lastname: Palomino-Segura
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, via Vincenzo Vela 6, 6500 Bellinzona, Switzerland.
authors.forename: Rocco
authors.initials: R
authors.lastname: D'Antuono
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, via Vincenzo Vela 6, 6500 Bellinzona, Switzerland; Institute of Computational Science, Università della Svizzera Italiana, via G. Buffi 13, 6900 Lugano, Switzerland.
authors.forename: Diego Ulisse
authors.initials: DU
authors.lastname: Pizzagalli
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, via Vincenzo Vela 6, 6500 Bellinzona, Switzerland; Institute for Microbiology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
authors.affiliation: Department of Internal Medicine II, Saarland University Medical Centre, 66424 Homburg, Germany.
authors.forename: Veronika
authors.initials: V
authors.lastname: Lukacs-Kornek
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, via Vincenzo Vela 6, 6500 Bellinzona, Switzerland; Department of Biomedical Sciences, Humanitas University, Via Manzoni 113, 20089 Rozzano-Milan, Italy.
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Uguccioni
authors.affiliation: Humabs BioMed SA, 6500 Bellinzona, Switzerland.
authors.forename: Davide
authors.initials: D
authors.lastname: Corti
authors.affiliation: Cancer Immunology, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Shannon J
authors.initials: SJ
authors.lastname: Turley
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, via Vincenzo Vela 6, 6500 Bellinzona, Switzerland; Institute for Microbiology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
authors.affiliation: Department of Pediatrics, Harvard Medical School and PCMM, Boston Childrens Hospital, Boston, MA 02115, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Carroll
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, via Vincenzo Vela 6, 6500 Bellinzona, Switzerland. Electronic address: santiago.gonzalez@irb.usi.ch.
authors.forename: Santiago F
authors.initials: SF
authors.lastname: Gonzalez
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D016923:Cell Death; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology*; D056724:Immunity, Humoral; D007249:Inflammation / Q000473:pathology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016899:Interferon-beta / Q000378:metabolism; D053582:Interleukin-1alpha / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000473:pathology* / Q000821:virology*; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D014611:Vaccination; D053586:Virus Internalization
chemical_list: D007252:Influenza Vaccines; D053582:Interleukin-1alpha; D053594:Myeloid Differentiation Factor 88; D051199:Toll-Like Receptor 7; D016899:Interferon-beta
keywords: CD11b(+) DC; IFN-β; IL-1α; MCP-1; alarmin; cytokine storm; inflammatory cascade; influenza; lymph node macrophages; vaccine