Mice Deficient in Interferon-Gamma or Interferon-Gamma Receptor 1 Have Distinct Inflammatory Responses to Acute Viral Encephalomyelitis

Eun Young Lee, Kimberly L W Schultz, Diane Griffin

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere76412
JournalPLoS One
Volume8
Issue number10
DOIs
StatePublished - Oct 24 2013

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viral encephalitis
Encephalomyelitis
interferon-gamma
Interferon-gamma
inflammation
Inbred C57BL Mouse
receptors
mice
Viruses
Fibroblasts
Messenger RNA
Antiviral Agents
Interleukin-6
Central Nervous System Viral Diseases
Tumor Necrosis Factor-alpha
Sindbis Virus
Alphavirus
interleukin-6
infection
Perforin

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Mice Deficient in Interferon-Gamma or Interferon-Gamma Receptor 1 Have Distinct Inflammatory Responses to Acute Viral Encephalomyelitis. / Lee, Eun Young; Schultz, Kimberly L W; Griffin, Diane.

In: PLoS One, Vol. 8, No. 10, e76412, 24.10.2013.

Research output: Contribution to journalArticle

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