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

Chatziandreou, Nikolaos; Farsakoglu, Yagmur; Palomino-Segura, Miguel; D’Antuono, Rocco; Pizzagalli, Diego Ulisse; Sallusto, Federica; Lukacs-Kornek, Veronika; Uguccioni, Mariagrazia; Corti, Davide; Turley, Shannon J.; Lanzavecchia, Antonio; Carroll, Michael C.; Gonzalez, Santiago F.

doi:10.1016/j.celrep.2017.02.026

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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

07.03.2017

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Cell reports. - 2017, vol. 18, no. 10, p. 2427-2440

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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