Respiratory viruses induce the expression of type I and III IFNs in MSCs through RLR/IRF3 signaling pathways

Mesenchymal stem cells (MSCs) comprise a primitive cell population and reside in various tissues and organs. These cells exhibit immunomodulatory activity and are effective in treating respiratory viral infections. The activation of type I and III interferons, which protect cells against viral infections, can be induced after pattern recognition receptors (PRRs) recognize viral nucleic acid species. Although certain viruses can upregulate IFN-b expression in MSCs, the underlying mechanisms and responsiveness to different IFNs are unclear. We found that foreskin-derived fibroblast-like stromal cells (FDSCs), a kind of functional MSC, were permissive to IAV PR8, HCoV-229E, and EV-D68. Infection by IAV PR8 and HCoV229E increased the expression of IFN-b and IFN-l species in FDSCs in an IRF-3-dependent manner. RIG-I was critical for detecting IAV PR8 in FDSCs, and IAV PR8 infection induced a significant increase in the expression of interferon signaling genes (ISGs). Interestingly, only IFN-b, but not IFN-l species, could induce the expression of ISGs, a finding supported by our observation that only IFN-b induced STAT1 and STAT2 phosphorylation in FDSCs. We also proved that treatment with IFN-b suppressed the propagation of IAV PR8 and promoted the survival of virus-infected FDSCs. Respiratory viruses could infect FDSCs and induce the expression of IFN-b and IFN-l1, but only IFN-b could protect FDSCs against viral infection. (c) 2023 The Authors. Published by Elsevier Masson SAS on behalf of Institut Pasteur. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Mesenchymal stem cells (MSCs) have immunomodulatory activity and are effective in treating respiratory viral infections. Infection by IAV PR8 and HCoV229E can increase the expression of IFN-b and IFN-l species in MSCs, and only IFN-b can protect MSCs against viral infection.