title: Murine gammaherpesvirus-68 elicits robust levels of interleukin-12 p40, but not interleukin-12 p70 production, by murine microglia and astrocytes.
abstract: Murine gammaherpesvirus-68 (gamma HV-68) is a tractable model to investigate the pathophysiology of human gammaherpesvirus infections, including Epstein-Barr virus (EBV). Herpesvirus infections are thought to play a role in the pathology of damaging, inflammatory diseases states of the central nervous system (CNS), such as multiple sclerosis. The ability of the host to mount a strong cell-mediated immune response is critical in determining the outcome of viral infections. Interleukin (IL)-12 is an important inflammatory cytokine that plays a pivotal role in the development of protective cell-mediated immune responses to viral infections. Given recent reports of associations between gammaherpesvirus infections and inflammatory disorders of the CNS, the authors investigated the ability of gamma HV-68 to induce the production of bioactive IL-12 in resident CNS cell types. In the present study, the authors demonstrate that gamma HV-68 infection is a potent stimulus for IL-12p40 production by murine microglia and astrocytes. However, despite the elevated expression of mRNA encoding IL-12p40 subunit, concomitant with robust secretion of IL-12p40 protein, gamma HV-68 failed to elicit the production of the bioactive IL-12p70 heterodimer. This failure did not result from an absence of T lymphocyte-derived signals or interactions between CNS cell types as determined by coculture studies. Taken together, these data suggest that the resident CNS cell types, astrocytes and microglia, are not significant sources of proinflammatory IL-12p70 in response to gammaherpesvirus infection. Indeed, the production of IL-12p40 may point to an anti-inflammatory role for these cells during herpesvirus infections of the CNS.
authors.affiliation: Department of Biology, University of North Carolina at Charlotte, 28223, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Rasley
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Bost
authors.forename: Ian
authors.initials: I
authors.lastname: Marriott
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000821:virology*; D001921:Brain / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D018142:Gammaherpesvirinae / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology*; D018664:Interleukin-12 / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40; D051379:Mice; D017628:Microglia / Q000276:immunology / Q000821:virology*; D021122:Protein Subunits / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D012333:RNA, Messenger; D018664:Interleukin-12