Subcapsular sinus macrophages promote NK cell accumulation and activation in response to lymph-borne viral particles.
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.
Institut Pasteur, Dynamics of Immune Responses Unit, Paris, France.
Zacarias
Z
Garcia
Fabrice
F
Lemaître
Nico
N
van Rooijen
Matthew L
ML
Albert
Yves
Y
Levy
Olivier
O
Schwartz
Philippe
P
Bousso
D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D019409:Interleukin-15 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008196:Lymph / Q000276:immunology* / Q000821:virology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D019713:Receptors, CCR5 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D054367:Receptors, CXCR3 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D011995:Recombination, Genetic; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology / Q000502:physiology; D014765:Viral Vaccines / Q000276:immunology; D014771:Virion / Q000276:immunology* / Q000502:physiology
D000950:Antigens, Ly; C515188:Cxcr3 protein, mouse; D019409:Interleukin-15; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D014765:Viral Vaccines; D049452:Green Fluorescent Proteins; D053633:Receptor, Interferon alpha-beta