Interleukin (IL)-12 receptor beta1 or IL-12 receptor beta 2 deficiency in mice indicates that IL-12 and IL-23 are not essential for host recovery from viral encephalitis.
Vesicular stomatitis virus (VSV), a negative-sense, single-stranded RNA rhabdovirus, causes acute viral encephalitis when administered intranasally to mice. Interleukin-12 (IL-12) is a key pro-inflammatory cytokine that is produced largely by the antigen presenting cells (APC) and that bridges the innate and acquired immune responses. IL-12 is efficacious in enhancing recovery from VSV infection of the murine central nervous system. This effect is mediated by nitric oxide (NO) produced by the neuronal isoform of nitric oxide synthase (NOS-1), and is independent of the pro-inflammatory cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). These data implied a link between IL-12 and NOS-1. Here we investigate the role of the IL-12R during VSV pathogenesis, using IL-12R beta2 and IL-12R beta1-deficient mice. We showed that a deficiency in either IL-12R beta2 or IL-12R beta1 had no effect on the outcome of VSV infection of the CNS or on the clearance of VSV from the CNS. Furthermore, these data indicate that IL-23 is not acting redundantly in the absence of IL-12 during VSV-induced encephalitis.
Ireland
Derek D C
DD
Department of Biology, New York University, New York, New York 10003-6688,
Palian
Beth M
BM
Reiss
Carol Shoshkes
CS
D000818:Animals; D018792:Encephalitis, Viral / Q000276:immunology* / Q000821:virology; D005260:Female; D018664:Interleukin-12 / Q000378:metabolism*; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018123:Receptors, Interleukin / Q000172:deficiency* / Q000235:genetics; D053707:Receptors, Interleukin-12; D018353:Rhabdoviridae Infections / Q000276:immunology / Q000821:virology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology / Q000472:pathogenicity*
C508440:Il12rb1 protein, mouse; C508443:Il12rb2 protein, mouse; C508841:Il23a protein, mouse; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12