Mice deficient in interferon-gamma or interferon-gamma receptor 1 have distinct inflammatory responses to acute viral encephalomyelitis

Interferon (IFN)-gamma is an important component of the immune response to viral infections that can have a role both in controlling virus replication and inducing inflammatory damage. To determine the role of IFN-gamma in fatal alphavirus encephalitis, we have compared the responses of wild type C5...

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Bibliographic Details
Published in:PloS one 2013-10, Vol.8 (10), p.e76412-e76412
Main Authors: Lee, Eun-Young, Schultz, Kimberly L W, Griffin, Diane E
Format: Article
Language:English
Subjects:
Alphavirus Infections - genetics
Alphavirus Infections - immunology
Alphavirus Infections - virology
Animals
Brain
Brain - metabolism
Brain - pathology
Brain - virology
CD3 antigen
Central nervous system
CXCL10 protein
Cytokines - genetics
Cytokines - metabolism
Disease Models, Animal
Embryos
Encephalitis
Encephalomyelitis
Encephalomyelitis - genetics
Encephalomyelitis - immunology
Encephalomyelitis - mortality
Encephalomyelitis - pathology
Encephalomyelitis - virology
Fibroblasts
Fibroblasts - metabolism
Fibroblasts - virology
Gene expression
Histocompatibility Antigens Class I - immunology
Histocompatibility Antigens Class I - metabolism
Histocompatibility Antigens Class II - immunology
Histocompatibility Antigens Class II - metabolism
Immune clearance
Immune response
Immune system
Immunology
Infections
Inflammation
Inflammatory response
Interferon
Interferon gamma Receptor
Interferon-gamma - deficiency
Interferon-gamma - genetics
Interferon-gamma - metabolism
Interleukin 6
Kinases
Lymphocytes
Lymphocytes T
Major histocompatibility complex
Mice
Mice, Knockout
Mortality
mRNA
Neurosciences
Paralysis
Pathogenesis
Perforin
Public health
Receptors, Interferon - deficiency
Receptors, Interferon - genetics
Receptors, Interferon - metabolism
Signal Transduction
Sindbis Virus - physiology
Spinal cord
Tumor necrosis factor-α
Viral infections
Viral Nonstructural Proteins - metabolism
Virus Replication
Viruses
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Summary:Interferon (IFN)-gamma is an important component of the immune response to viral infections that can have a role both in controlling virus replication and inducing inflammatory damage. To determine the role of IFN-gamma in fatal alphavirus encephalitis, we have compared the responses of wild type C57BL/6 (WTB6) mice with mice deficient in either IFN-gamma (GKO) or the alpha-chain of the IFN-gamma receptor (GRKO) after intranasal infection with a neuroadapted strain of sindbis virus. Mortalities of GKO and GRKO mice were similar to WTB6 mice. Both GKO and GRKO mice had delayed virus clearance from the brain and spinal cord, more infiltrating perforin(+) cells and lower levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 mRNAs than WTB6 mice. However, inflammation was more intense in GRKO mice than WTB6 or GKO mice with more infiltrating CD3(+) T cells, greater expression of major histocompatibility complex-II and higher levels of interleukin-17A mRNA. Fibroblasts from GRKO embryos did not develop an antiviral response after treatment with IFN-gamma, but showed increases in TNF-alpha, IL-6, CXCL9 and CXCL10 mRNAs although these increases developed more slowly and were less intense than those of WTB6 fibroblasts. These data indicate that both GKO and GRKO mice fail to develop an IFN-gamma-mediated antiviral response, but differ in regulation of the inflammatory response to infection. Therefore, GKO and GRKO cannot be considered equivalent when assessing the role of IFN-gamma in CNS viral infections.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0076412