1. Virus-Infected Human Mast Cells Enhance Natural Killer Cell Functions
- Author
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Ian D. Haidl, Patrick W.K. Lee, Jean S. Marshall, and Liliana Portales-Cervantes
- Subjects
0301 basic medicine ,Cytotoxicity, Immunologic ,Orthoreovirus, Mammalian ,Mice, SCID ,Receptor, Interferon alpha-beta ,Biology ,Natural killer cell ,03 medical and health sciences ,Mice ,Paracrine Communication ,medicine ,Immunology and Allergy ,Animals ,Humans ,Mast Cells ,Immunity, Mucosal ,Cells, Cultured ,Lymphokine-activated killer cell ,Degranulation ,Interleukin-18 ,Natural killer T cell ,Mast cell ,Fetal Blood ,Cell biology ,Reoviridae Infections ,Interleukin 33 ,Killer Cells, Natural ,030104 developmental biology ,medicine.anatomical_structure ,Interleukin 15 ,Organ Specificity ,Tumor necrosis factor alpha ,Interferons - Abstract
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.
- Published
- 2016