Conditioned medium from persistently RSV-infected macrophages alters transcriptional profile and inflammatory response of non-infected macrophages

• Published in: Virus research 2017-02, Vol.230, p.29-37
• Main Authors: Rivera-Toledo, Evelyn, Salido-Guadarrama, Iván, Rodríguez-Dorantes, Mauricio, Torres-González, Laura, Santiago-Olivares, Carlos, Gómez, Beatriz
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; Conditioned medium; Culture Media, Conditioned - pharmacology; Gene Expression Profiling; Gene Expression Regulation; Host-Pathogen Interactions; Inflammasomes - antagonists & inhibitors; Inflammasomes - genetics; Inflammasomes - immunology; Interleukin-1beta - antagonists & inhibitors; Interleukin-1beta - genetics; Interleukin-1beta - immunology; Macrophage Activation - drug effects; Macrophages - immunology; Macrophages - secretion; Macrophages - virology; Mice; Microarray; NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - immunology; NLRP3 inflammasome; Respiratory syncytial virus; Respiratory Syncytial Viruses - growth & development; Respiratory Syncytial Viruses - pathogenicity; Signal Transduction; Transcription, Genetic - drug effects; Transcriptome; Viral persistence
• ISSN: 0168-1702; 1872-7492
• DOI: 10.1016/j.virusres.2017.01.001

A new gene-transcription pattern is induced in non-infected macrophages after exposure to conditioned medium from persistently RSV-infected macrophages. Those “conditioned” non-infected MΦ display a potentiated inflammatory response mediated by the NLRP3-inflammasome upon viral infection, in contrast to non-conditioned macrophages (some images from: www.somersault1824.com). [Display omitted] •RSV persistence induced expression of pro-inflammatory mediators in host macrophages.•Soluble factors from persistently RSV-infected cells altered gene transcription in non-infected cells.•Altered transcription involved an antiviral state and exacerbated inflammatory response. Cells susceptible to persistent viral infections undergo important changes in their biological functions as a consequence of the expression of viral gene products that are capable of altering the gene expression profile of the host cell. Previously, we reported that persistence of the RSV genome in a mouse macrophage cell line induces important alterations in cell homeostasis, including constitutive expression of IFN-β and other pro-inflammatory cytokines. Here, we postulated that changes in the homeostasis of non-infected macrophages could be induced by soluble factors secreted by persistently RSV- infected macrophages. To test this hypothesis, non-infected mouse macrophages were treated with conditioned medium (CM) collected from cultures of persistently RSV-infected macrophages. Total RNA was extracted and a microarray-based gene expression analysis was performed. Non-infected macrophages, treated under similar conditions with CM obtained from cultures of non-infected macrophages, were used as a control to establish differential gene expression between the two conditions. Results showed that CM from the persistently RSV-infected cultures altered expression of a total of 95 genes in non-infected macrophages, resulting in an antiviral gene-transcription profile along with inhibition of the inflammatory response, since some inflammatory genes were down-regulated, including Nlrp3 and Il-1 β, both related to the inflammasome pathway. However, down-regulation of Nlrp3 and Il-1 β was reversible upon acute RSV infection. Additionally, we observed that the inflammatory response, evaluated by secreted IL-1 β, a final product of the inflammasome activity, was enhanced during acute RSV infection in macrophages treated with CM from persistently RSV-infected cultures, compared to that in macrophages treate