IFN-lambda (IFN-lambda) Is Expressed in a Tissue-Dependent Fashion and Primarily Acts on Epithelial Cells in Vivo

PLoS Pathog. 2008 Mar 14;4(3):e1000017. doi: 10.1371/journal.ppat.1000017.

Abstract

Interferons (IFN) exert antiviral, immunomodulatory and cytostatic activities. IFN-alpha/beta (type I IFN) and IFN-lambda (type III IFN) bind distinct receptors, but regulate similar sets of genes and exhibit strikingly similar biological activities. We analyzed to what extent the IFN-alpha/beta and IFN-lambda systems overlap in vivo in terms of expression and response. We observed a certain degree of tissue specificity in the production of IFN-lambda. In the brain, IFN-alpha/beta was readily produced after infection with various RNA viruses, whereas expression of IFN-lambda was low in this organ. In the liver, virus infection induced the expression of both IFN-alpha/beta and IFN-lambda genes. Plasmid electrotransfer-mediated in vivo expression of individual IFN genes allowed the tissue and cell specificities of the responses to systemic IFN-alpha/beta and IFN-lambda to be compared. The response to IFN-lambda correlated with expression of the alpha subunit of the IFN-lambda receptor (IL-28R alpha). The IFN-lambda response was prominent in the stomach, intestine and lungs, but very low in the central nervous system and spleen. At the cellular level, the response to IFN-lambda in kidney and brain was restricted to epithelial cells. In contrast, the response to IFN-alpha/beta was observed in various cell types in these organs, and was most prominent in endothelial cells. Thus, the IFN-lambda system probably evolved to specifically protect epithelia. IFN-lambda might contribute to the prevention of viral invasion through skin and mucosal surfaces.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / virology
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Cytokines / immunology
  • Disease Models, Animal
  • Epithelial Cells / metabolism*
  • Epithelial Cells / virology
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Gene Expression Regulation, Viral
  • Kidney / metabolism
  • Kidney / virology
  • Liver / metabolism
  • Liver / virology
  • Male
  • Mice
  • Mice, Congenic
  • Mice, Inbred C57BL
  • Organ Specificity
  • RNA Viruses / immunology
  • RNA, Messenger / metabolism
  • RNA, Viral / analysis

Substances

  • Cytokines
  • RNA, Messenger
  • RNA, Viral
  • interferon-lambda protein, mouse