The bone marrow is patrolled by NK cells that are primed and expand in response to systemic viral activation

Eur J Immunol. 2018 Jul;48(7):1137-1152. doi: 10.1002/eji.201747378. Epub 2018 May 2.

Abstract

The bone marrow hosts NK cells whose distribution, motility and response to systemic immune challenge are poorly understood. At steady state, two-photon microscopy of the bone marrow in Ncr1gfp/+ mice captured motile NK cells interacting with dendritic cells. NK cells expressed markers and effector molecules of mature cells. Following poly (I:C) injection, RNA-Seq of NK cells revealed three phases of transcription featuring immune response genes followed by posttranscriptional processes and proliferation. Functionally, poly (I:C) promoted upregulation of granzyme B, enhanced cytotoxicity in vitro and in vivo, and, in the same individual cells, triggered proliferation. Two-photon imaging revealed that the proportion of sinusoidal NK cells decreased, while at the same time parenchymal NK cells accelerated, swelled and divided within the bone marrow. MVA viremia induced similar responses. Our findings demonstrate that the bone marrow is patrolled by mature NK cells that rapidly proliferate in response to systemic viral challenge while maintaining their effector functions.

Keywords: Bone marrow; Cell migration; Cellular proliferation; NK cells; Two-photon imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / genetics
  • Bone Marrow / immunology*
  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Cytotoxicity, Immunologic
  • Dendritic Cells / immunology*
  • Granzymes / metabolism
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Natural Cytotoxicity Triggering Receptor 1 / genetics
  • Poly I-C / immunology
  • Viremia / immunology*
  • Virus Activation

Substances

  • Antigens, Ly
  • Natural Cytotoxicity Triggering Receptor 1
  • Ncr1 protein, mouse
  • Granzymes
  • Poly I-C