IFN-lambda (IFN-lambda) is expressed in a tissue-dependent fashion and primarily acts on epithelial cells in vivo.
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.
Sommereyns
Caroline
C
Université catholique de Louvain, de Duve Institute, MIPA-VIRO 74-49, Brussels, Belgium.
Paul
Sophie
S
Staeheli
Peter
P
Michiels
Thomas
T
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000821:virology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism* / Q000821:virology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015967:Gene Expression Regulation, Viral; D007668:Kidney / Q000378:metabolism / Q000821:virology; D008099:Liver / Q000378:metabolism / Q000821:virology; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D012328:RNA Viruses / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000032:analysis; D007378:Interleukins; D000095022:Interferon Lambda
D016207:Cytokines; D012333:RNA, Messenger; D012367:RNA, Viral; C511668:interferon-lambda protein, mouse; D007378:Interleukins; D000095022:Interferon Lambda