Human mast cell interferon responses and survival in the context of Coronavirus and Respiratory Syncytial Virus are enhanced by IL-5

Mast cells have been shown to be important sentinel cells in multiple models of viral and bacterial infection. Exacerbations of allergic asthma and asthma deaths are often associated with respiratory viral infections. Elevated levels of type 2 cytokines, especially interleukin 5 (IL-5), are also associated with allergic disease and have been targeted therapeutically. Here, we demonstrate that IL-5 signaling enhances the ability of human mast cells to mount a potent anti-viral response against respiratory viruses. Mast cells derived from umbilical cord-blood, treated with IL-5 and infected with respiratory viruses such as the human Coronavirus OC43 or respiratory syncytial virus (RSV) produced significantly more type I and type III interferons (IFNs) than non-IL-5 treated controls. IL-5 treatment also led to greater expression of IFN stimulated genes and upregulated expression of the pro-survival factor B-cell lymphoma 2 (BCL2) and protected mast cells from apoptosis-induced stress. IL-5 also upregulated expression of Endothelial PAS Domain Protein 1 (EPAS1), demonstrating an important IL-5 driven pro-survival network in mast cells. These resultssuggest an unexpected role for IL-5 signaling in regulating mast cell interferon responses and maintaining mast cell populations during mucosal viral infection. Overall design: Umbilical cord blood-derived mast cells (CBMCs) from 8 donors were treated them with 10 ng/mL of human IL-5 and 100 ng/mL of human SCF for 24 hours and with 10 ng/mL of human IL-5 and 10 ng/mL human SCF for 18 hours prior to RNA harvest. Gene expression in these samples was compared to that in another set of CBMCs from 8 donors who only received a mock treatment (media).