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Cell Rep. 2017 Mar 7;18(10):2427-2440. doi: 10.1016/j.celrep.2017.02.026.

Macrophage Death following Influenza Vaccination Initiates the Inflammatory Response that Promotes Dendritic Cell Function in the Draining Lymph Node.

Author information

1
Institute for Research in Biomedicine, Università della Svizzera Italiana, via Vincenzo Vela 6, 6500 Bellinzona, Switzerland.
2
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.
3
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.
4
Department of Internal Medicine II, Saarland University Medical Centre, 66424 Homburg, Germany.
5
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.
6
Humabs BioMed SA, 6500 Bellinzona, Switzerland.
7
Cancer Immunology, Genentech, South San Francisco, CA 94080, USA.
8
Department of Pediatrics, Harvard Medical School and PCMM, Boston Childrens Hospital, Boston, MA 02115, USA.
9
Institute for Research in Biomedicine, Università della Svizzera Italiana, via Vincenzo Vela 6, 6500 Bellinzona, Switzerland. Electronic address: santiago.gonzalez@irb.usi.ch.

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.

KEYWORDS:

CD11b(+) DC; IFN-β; IL-1α; MCP-1; alarmin; cytokine storm; inflammatory cascade; influenza; lymph node macrophages; vaccine

PMID:
28273457
DOI:
10.1016/j.celrep.2017.02.026
[Indexed for MEDLINE]
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