Subcapsular sinus macrophages promote NK cell accumulation and activation in response to lymph-borne viral particles.

Zacarias Garcia (1, 2) , Fabrice Lemaître (1, 2) , Nico van Rooijen (3) , Matthew L Albert (4) , Yves Levy (5, 2) , Olivier Schwartz (6, 2) , Philippe Bousso (1, 2)

1 Dynamiques des Réponses Immunes
2 VRI - Vaccine Research Institute
3 Department of Molecular Cell Biology [Amsterdam UMC]
4 Immunobiologie des Cellules Dendritiques
5 IMRB - Institut Mondor de Recherche Biomédicale
6 Virus et Immunité

Natural killer (NK) cells become activated during viral infection in response to cytokines or to engagement of NK cell activating receptors. However, the identity of cells sensing viral particles and mediating NK cell activation has not been defined. Here, we show that local administration of a modified vaccinia virus Ankara vaccine in mice results in the accumulation of NK cells in the subcapsular area of the draining lymph node and their activation, a process that is strictly dependent on type I IFN signaling. NK cells located in the subcapsular area exhibited reduced motility and were found associated with CD169(+)-positive subcapsular sinus (SCS) macrophages and collagen fibers. Moreover, depletion of SCS macrophages using clodronate liposomes abolished NK cell accumulation and activation. Our results identify SCS macrophages as primary mediators of NK cell activation in response to lymph-borne viral particles suggesting that they act as early sensors of local infection or delivery of viral-based vaccines.

Domains: Life Sciences [q-bio]; Innate immunity

Zacarias Garcia, Fabrice Lemaître, Nico van Rooijen, Matthew L Albert, Yves Levy, et al.. Subcapsular sinus macrophages promote NK cell accumulation and activation in response to lymph-borne viral particles.. Blood, 2012, 120 (24), pp.4744-50. ⟨10.1182/blood-2012-02-408179⟩. ⟨pasteur-01110078⟩