Dynamic Expression of Interferon Lambda Regulated Genes in Primary Fibroblasts and Immune Organs of the Chicken

Genes (Basel). 2019 Feb 14;10(2):145. doi: 10.3390/genes10020145.

Abstract

Interferons (IFNs) are pleiotropic cytokines that establish a first line of defense against viral infections in vertebrates. Several types of IFN have been identified; however, limited information is available in poultry, especially using live animal experimental models. IFN-lambda (IFN-λ) has recently been shown to exert a significant antiviral impact against viral pathogens in mammals. In order to investigate the in vivo potential of chicken IFN-λ (chIFN-λ) as a regulator of innate immunity, and potential antiviral therapeutics, we profiled the transcriptome of chIFN-λ-stimulated chicken immune organs (in vivo) and compared it with primary chicken embryo fibroblasts (in vitro). Employing the baculovirus expression vector system (BEVS), recombinant chIFN-λ3 (rchIFN-λ3) was produced and its biological activities were demonstrated. The rchIFNλ3 induced a great array of IFN-regulated genes in primary chicken fibroblast cells. The transcriptional profiling using RNA-seq and subsequent bioinformatics analysis (gene ontology, differential expressed genes, and KEGGs analysis) of the bursa of Fabricious and the thymus demonstrated an upregulation of crucial immune genes (viperin, IKKB, CCL5, IL1β, and AP1) as well as the antiviral signaling pathways. Interestingly, this experimental approach revealed contrasting evidence of the antiviral potential of chIFN-λ in both in vivo and in vitro models. Taken together, our data signifies the potential of chIFN-λ as a potent antiviral cytokine and highlights its future possible use as an antiviral therapeutic in poultry.

Keywords: ISGs; RNA-Seq; Transcriptome; antiviral pathway; interferon lambda.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Bursa of Fabricius / immunology
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / immunology
  • Chick Embryo
  • Chickens / genetics
  • Chickens / immunology*
  • Cytokines / genetics*
  • Fibroblasts / drug effects
  • Fibroblasts / immunology
  • Genes, Regulator / genetics
  • Immunity, Innate / genetics*
  • Interferons / genetics*
  • Thymus Gland / immunology
  • Virus Replication / genetics
  • Virus Replication / immunology

Substances

  • Antiviral Agents
  • Chemokine CCL5
  • Cytokines
  • Interferons