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

Mohamed Habbeddine, Christophe Verthuy, Olivia Rastoin, Lionel Chasson, Magali Bebien, Marc Bajenoff, Sahil Adriouch, Joke M.M. den Haan, Josef M. Penninger, Toby Lawrence*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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. Habbeddine et al. show that RANK signaling in the spleen marginal zone plays an important role in orchestrating protective immune responses to viral infection. They show that RANK expressed by macrophages supports viral replication, while RANK signaling in dendritic cells promotes the recruitment and activation of memory CD8 T cells.

Original languageEnglish
Pages (from-to)2515-2527
Number of pages13
JournalCell Reports
Volume21
Issue number9
DOIs
Publication statusPublished - 28 Nov 2017

Cite this

Habbeddine, M., Verthuy, C., Rastoin, O., Chasson, L., Bebien, M., Bajenoff, M., ... Lawrence, T. (2017). Receptor Activator of NF-κB Orchestrates Activation of Antiviral Memory CD8 T Cells in the Spleen Marginal Zone. Cell Reports, 21(9), 2515-2527. https://doi.org/10.1016/j.celrep.2017.10.111