Virus-Infected Human Mast Cells Enhance Natural Killer Cell Functions

J Innate Immun. 2017;9(1):94-108. doi: 10.1159/000450576. Epub 2016 Nov 3.


Mucosal surfaces are protected from infection by both structural and sentinel cells, such as mast cells. The mast cell's role in antiviral responses is poorly understood; however, they selectively recruit natural killer (NK) cells following infection. Here, the ability of virus-infected mast cells to enhance NK cell functions was examined. Cord blood-derived human mast cells infected with reovirus (Reo-CBMC) and subsequent mast cell products were used for the stimulation of human NK cells. NK cells upregulated the CD69 molecule and cytotoxicity-related genes, and demonstrated increased cytotoxic activity in response to Reo-CBMC soluble products. NK cell interferon (IFN)-γ production was also promoted in the presence of interleukin (IL)-18. In vivo, SCID mice injected with Reo-CBMC in a subcutaneous Matrigel model, could recruit and activate murine NK cells, a property not shared by normal human fibroblasts. Soluble products of Reo-CBMC included IL-10, TNF, type I and type III IFNs. Blockade of the type I IFN receptor abrogated NK cell activation. Furthermore, reovirus-infected mast cells expressed multiple IFN-α subtypes not observed in reovirus-infected fibroblasts or epithelial cells. Our data define an important mast cell IFN response, not shared by structural cells, and a subsequent novel mast cell-NK cell immune axis in human antiviral host defense.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytotoxicity, Immunologic
  • Fetal Blood / cytology
  • Humans
  • Immunity, Mucosal*
  • Interferons / metabolism
  • Interleukin-18 / metabolism
  • Killer Cells, Natural / immunology*
  • Mast Cells / immunology*
  • Mast Cells / transplantation
  • Mast Cells / virology
  • Mice
  • Mice, SCID
  • Organ Specificity
  • Orthoreovirus, Mammalian / immunology*
  • Paracrine Communication
  • Receptor, Interferon alpha-beta / antagonists & inhibitors
  • Reoviridae Infections / immunology*


  • Interleukin-18
  • Receptor, Interferon alpha-beta
  • Interferons