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Cell Rep. 2017 Nov 28;21(9):2515-2527. doi: 10.1016/j.celrep.2017.10.111.

Receptor Activator of NF-κB Orchestrates Activation of Antiviral Memory CD8 T Cells in the Spleen Marginal Zone.

Author information

1
Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, Inserm, CNRS, Marseille, France.
2
Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, 76183 Rouen, France; Institut National de la Santé et de la Recherche Médicale (Inserm), U905, 76183 Rouen, France.
3
Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1007 MB Amsterdam, the Netherlands.
4
Institute of Molecular Biotechnology (IMBC), Austrian Academy of Sciences, 1030 Vienna, Austria.
5
Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, Inserm, CNRS, Marseille, France. Electronic address: lawrence@ciml.univ-mrs.fr.

Abstract

The spleen plays an important role in protective immunity to bloodborne pathogens. Macrophages and dendritic cells (DCs) in the spleen marginal zone capture microbial antigens to trigger adaptive immune responses. Marginal zone macrophages (MZMs) can also act as a replicative niche for intracellular pathogens, providing a platform for mounting the immune response. Here, we describe a role for RANK in the coordinated function of antigen-presenting cells in the spleen marginal zone and triggering anti-viral immunity. Targeted deletion of RANK results in the selective loss of CD169+ MZMs, which provide a niche for viral replication, while RANK signaling in DCs promotes the recruitment and activation of anti-viral memory CD8 T cells. These studies reveal a role for the RANKL/RANK signaling axis in the orchestration of protective immune responses in the spleen marginal zone that has important implications for the host response to viral infection and induction of acquired immunity.

KEYWORDS:

CD169; NF-κB; adaptive immunity; dendritic cells; inflammation; innate immunity; macrophages; marginal zone

PMID:
29186688
PMCID:
PMC5723674
DOI:
10.1016/j.celrep.2017.10.111
[Indexed for MEDLINE]
Free PMC Article

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