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Nat Med. 2016 Jan;22(1):64-71. doi: 10.1038/nm.4016. Epub 2015 Dec 21.

In vivo imaging of inflammasome activation reveals a subcapsular macrophage burst response that mobilizes innate and adaptive immunity.

Author information

1
Dynamics of Immune Responses Unit, Institut Pasteur, Paris, France.
2
Institut National de la Santé et de la Recherche Médicale U668, Paris, France.
3
Laboratory of Dendritic Cells Immunobiology, Institut Pasteur, Paris, France.
4
Institut National de la Santé et de la Recherche Médicale U818, Paris, France.
5
Vaccine Research Institute, Créteil, France.
6
Institut National de la Santé et de la Recherche Médicale U955, Créteil, France.
7
Faculté de Médecine, Université Paris Est, Créteil, France.
8
Service d'Immunologie Clinique et Maladies Infectieuses, Hôpital H. Mondor-A. Chenevier, Créteil, France.

Abstract

The inflammasome is activated in response to a variety of pathogens and has an important role in shaping adaptive immunity, yet the spatiotemporal orchestration of inflammasome activation in vivo and the mechanisms by which it promotes an effective immune response are not fully understood. Using an in vivo reporter to visualize inflammasome assembly, we establish the distribution, kinetics and propagation of the inflammasome response to a local viral infection. We show that modified vaccinia Ankara virus induces inflammasome activation in subcapsular sinus (SCS) macrophages, which is immediately followed by cell death and release of extracellular ASC specks. This transient inflammasome signaling in the lymph node generates a robust influx of inflammatory cells and mobilizes T cells from the circulation to increase the magnitude of T cell responses. We propose that after infection, SCS macrophages deliver a burst response of inflammasome activity and cell death that translates into the broadening of T cell responses, identifying an important aspect of inflammasome-driven vaccination strategies.

PMID:
26692332
DOI:
10.1038/nm.4016
[Indexed for MEDLINE]
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