Interleukin 27, like interferons, activates JAK-STAT signaling and promotes pro-inflammatory and antiviral states that interfere with dengue and chikungunya viruses replication in human macrophages

ABSTRACT: Interferons (IFNs) are a family of cytokines that activate the JAK-STAT signaling pathway to induce an antiviral state in cells. Interleukin 27 (IL-27) is a member of the IL-6 and/or IL-12 family that elicits both pro- and anti-inflammatory responses. Recent studies have reported that IL-27 also induces a robust antiviral response against diverse viruses, both in vitro and in vivo, suggesting that IFNs and IL-27 share many similarities at the functional level. However, it is still unknown how similar or different IFN- and IL-27-dependent signaling pathways are. To address this question, we conducted a comparative analysis of the transcriptomic profiles of human monocyte-derived macrophages (MDMs) exposed to IL-27 and those exposed to recombinant human IFN-a, IFN-g, and IFN-l. We utilized bioinformatics approaches to identify common differentially expressed genes between the different transcriptomes. To verify the accuracy of this approach, we used RT-qPCR, ELISA, flow cytometry, and microarrays data. We found that IFNs and IL-27 induce transcriptional changes in several genes, including those involved in JAK-STAT signaling, and induce shared pro-inflammatory and antiviral pathways in MDMs, leading to the common and unique expression of inflammatory factors and IFN-stimulated genes (ISGs)Importantly, the ability of IL-27 to induce those responses is independent of IFN induction and cellular lineage. Additionally, functional analysis demonstrated that like IFNs, IL-27-mediated response reduced chikungunya and dengue viruses replication in MDMs. In su summary, IL-27 exhibits properties similar to those of all three types of human IFN, including the ability to stimulate a protective antiviral response. Given this similarity, we propose that IL-27 could be classified as a distinct type of IFN, possibly categorized as IFN-pi (IFN-p), the type V IFN (IFN-V).

• Autores: Valdés López, Juan Felipe; Hernández Sarmiento, Lady Johana; Tamayo Molina, Yordi Sebastián; Velilla Hernández, Paula Andrea; Urcuqui Inchima, Silvio; Rodenhuis Zybert, Izabela A.
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2024
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/41430
• Acceso en línea: https://hdl.handle.net/10495/41430
• Palabra clave: Células Cultivadas; Cells, Cultured; Interleucina-27; Interleukin-27; Fiebre Chikungunya; Chikungunya Fever; Virus Chikungunya; Chikungunya virus; Virus del Dengue; Dengue Virus; Dengue; Interferones; Interferons; Interleucinas; Interleukins; Quinasas Janus; Janus Kinases; Macrófagos; Macrophages; Factores de Transcripción STAT; STAT Transcription Factors; Transducción de Señal; Signal Transduction; Replicación Viral; Virus Replication; https://id.nlm.nih.gov/mesh/D002646; https://id.nlm.nih.gov/mesh/D002478; https://id.nlm.nih.gov/mesh/D064094; https://id.nlm.nih.gov/mesh/D065632; https://id.nlm.nih.gov/mesh/D003716; https://id.nlm.nih.gov/mesh/D003715; https://id.nlm.nih.gov/mesh/D007372; https://id.nlm.nih.gov/mesh/D007378; https://id.nlm.nih.gov/mesh/D053612; https://id.nlm.nih.gov/mesh/D008264; https://id.nlm.nih.gov/mesh/D050791; https://id.nlm.nih.gov/mesh/D015398; https://id.nlm.nih.gov/mesh/D014779
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/