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. 2022 Jul 21;23(14):8038. doi: 10.3390/ijms23148038

Figure 3.

Figure 3

Infection of MSC by viruses may be controlled by a canonical innate immune response. Viruses may target perivascular MSC naturally expressing receptors (e.g., MXRA8/alphavirus) to grant entry. Among the up-regulated cytosolic pattern recognition receptors (PRRs), Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLR: RIG-I, Melanoma-Differentiation-Associated Gene-5 or MDA5) and Toll-Like Receptor 3 (TLR3) are important to detect viral RNA. After sensing, MSCs engage different cell signaling pathways according to the stimulated PRR. A TLR3-dependent sensing activates mitogen-activated protein kinase pathways (through p38 MAPK and p46 JNK). RLR-dependent sensing stimulates IFN signaling pathway through TBK1/IKK-ε and subsequent interferon regulatory factor (IRF) 7 phosphorylation. These signaling pathways both trigger the production of pro-inflammatory cytokines and peptides with antiviral activities. Hence, in viral context MSCs express increased levels of IL-1β, IL-6, IL-8, IL-11, IL-12p35, IL-23p19, IL-27p28, TNF-α and CCL5/RANTES to recruit and activate adaptive immune cells (T/B lymphocytes). Furthermore, MSCs produce IFN-β and IFN-λ1). Classically, type I IFNs (such as IFN-β) induce the expression of Interferon Stimulated Genes (ISGs, e.g., RNASEL) by the interaction with the IFN receptor (IFNAR).