Interleukin-27 expression following infection with the murine gammaherpesvirus 68.
IL-27 is a heterodimeric cytokine composed of p28 and Epstein Barr virus induced gene 3 (Ebi3) protein subunits. In the present study, we questioned whether murine gammaherpesvirus 68 (HV-68) could induce expression of Ebi3, p28, and IL-27 in this mouse model of an EBV-like infection. Cultured macrophages and dendritic cells exposed to HV-68 upregulated p28 mRNA expression and increased secretion of the p28 and IL-27 (p28+Ebi3) proteins. B220(+) and CD11b(+) cells also upregulated p28 mRNA expression following in vivo infection with this virus. Surprisingly, no significant increases in p28 or IL-27 protein production were observed in vivo during the acute or mononucleosis phases of the disease. The possibility that HV-68-induced upregulation of p28 mRNA expression primed cells for IL-27 secretion was suggested by the ability of a TLR4 agonist to augment cytokine production. When cultured macrophages and dendritic cells were exposed to virus plus a suboptimal dose of LPS, increased levels of p28 protein expression were observed. More importantly, when latently infected mice were challenged with a sublethal dose of LPS, augmented p28 and IL-27 protein production occurred. Using a model of sepsis, mice latently infected with HV-68 had exaggerated p28 protein production when compared to mice that were singularly infected or subjected to cecal ligation and puncture. Taken together, these studies define expression of HV-68 induced IL-27, and suggest that mice latently infected with this gammaherpesvirus will have exaggerated responses when confronted with other stimuli capable of inducing this member of the IL-12 family of cytokines.
Nelson
Daniel A
DA
Department of Biology, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC 28223, USA. danelson@uncc.edu
Tolbert
Melanie D
MD
Clemens
Mark G
MG
Bost
Kenneth L
KL
D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D006566:Herpesviridae Infections / Q000503:physiopathology*; D020381:Interleukin-17 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D021122:Protein Subunits / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D018121:Receptors, Cytokine / Q000096:biosynthesis*; D018144:Rhadinovirus / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000819:agonists; D014412:Tumor Virus Infections / Q000503:physiopathology*
C499601:Ebi3 protein, mouse; D020381:Interleukin-17; D008070:Lipopolysaccharides; D015778:Minor Histocompatibility Antigens; D021122:Protein Subunits; D012333:RNA, Messenger; D018121:Receptors, Cytokine; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4