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Journal article

Macrophage death following influenza vaccination initiates the inflammatory response that promotes dendritic cell function in the draining lymph node

  • Chatziandreou, Nikolaos Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Farsakoglu, Yagmur Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Palomino-Segura, Miguel Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • D’Antuono, Rocco Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Pizzagalli, Diego Ulisse Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Institute for Microbiology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland
  • Lukacs-Kornek, Veronika Department of Internal Medicine II, Saarland University Medical Centre, 66424 Homburg, Germany
  • Uguccioni, Mariagrazia Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Department of Biomedical Sciences, Humanitas University, Via Manzoni 113, 20089 Rozzano-Milan, Italy
  • Corti, Davide Humabs BioMed SA, 6500 Bellinzona, Switzerland
  • Turley, Shannon J. Cancer Immunology, Genentech, South San Francisco, CA 94080, USA
  • Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Institute for Microbiology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland
  • Carroll, Michael C. Department of Pediatrics, Harvard Medical School and PCMM, Boston Childrens Hospital, Boston, MA 02115, USA
  • Gonzalez, Santiago F. Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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    07.03.2017
Published in:
  • Cell reports. - 2017, vol. 18, no. 10, p. 2427-2440
IL-1α
Alarmin
Lymph node macrophages
Inflammatory cascade
Cytokine storm
IFN-β
Influenza
Caccine
CD11b+ DC
MCP-1
English 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.
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  • English
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Medicine
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https://n2t.net/ark:/12658/srd1319036
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