Interleukin-5 enhances human mast cell survival and interferon responses to viral infection.

in The Journal of allergy and clinical immunology by Jasmine Barra, Christopher R Liwski, Phoebe Phonchareon, Liliana Portales-Cervantes, Daniel Gaston, Tobias K Karakach, Ian D Haidl, Jean S Marshall

TLDR

  • This study found that IL-5 signaling promotes IFN responses in mast cells and maintains mast cell populations during mucosal viral infection via a novel IL-5/EPAS1 axis.

Abstract

Mast cells are important sentinel cells in defense against mucosal infection. Exacerbations of allergic asthma and asthma deaths have been associated with respiratory viral infections. Elevated levels of interleukin-5 (IL-5) have been associated with the pathogenesis of severe atopic diseases, many of which respond to IL-5 blockade. This study sought to examine the impact of IL-5 signaling on mast cells infected with respiratory viruses. Cord-blood derived human mast cells were treated with IL-5 or left untreated and infected with coronavirus OC43, respiratory syncytial virus (RSV), or oncolytic reovirus. Mast cell expression of interferons (IFN) and of IFN stimulated genes was evaluated. Total RNA sequencing was performed to determine the impact of IL-5 on the transcriptome of human mast cells and related functional assays were performed. IL-5 treated mast cells produced significantly more type I and type III IFNs than non-IL-5 treated controls. Mechanistically, IL-5 treatment led to greater expression of the pro-survival factor B-cell lymphoma 2 (BCL2) and Endothelial PAS Domain Protein 1 (EPAS1), and protected mast cells from apoptosis-induced stress. IL-5 blockade was associated with a decrease in EPAS1 expression in the peripheral blood of asthmatic patients as shown by transcriptomic data from clinical trials of mepolizumab and benralizumab. IL-5 signaling selectively promotes IFN responses in mast cells and maintains mast cell populations during mucosal viral infection via a novel IL-5/EPAS1 axis.

Overview

  • This study aimed to investigate the impact of interleukin-5 (IL-5) signaling on mast cells infected with respiratory viruses.
  • Cord-blood derived human mast cells were treated with IL-5 or left untreated and infected with coronavirus OC43, respiratory syncytial virus (RSV), or oncolytic reovirus.
  • The study sought to understand the role of IL-5 in modulating mast cell responses to viral infections, with potential implications for the treatment of allergic asthma.

Comparative Analysis & Findings

  • IL-5 treated mast cells produced significantly more type I and type III IFNs than non-IL-5 treated controls.
  • IL-5 treatment led to greater expression of the pro-survival factor BCL2 and Endothelial PAS Domain Protein 1 (EPAS1).
  • IL-5 blockade was associated with a decrease in EPAS1 expression in the peripheral blood of asthmatic patients.

Implications and Future Directions

  • The study's findings suggest that IL-5 targeting therapies may be beneficial in the treatment of allergic asthma by modulating mast cell responses to viral infections.
  • Further studies are needed to explore the relationship between IL-5 and EPAS1 in human disease, and to investigate the potential therapeutic applications of this axis.
  • The study highlights the importance of considering the mucosal environment and the interactions between immune cells, viruses, and the epithelium in the development of treatments for respiratory diseases.
Read Full Article