IRF3 deficiency impacts granzyme B expression and maintenance of memory T cell function in response to viral infection

Tyler C. Moore, Alexander J. Vogel, Thomas M Petro, Deborah M Brown

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The role of interferon regulatory factor 3 (IRF3) in the innate immune response to infection has been well studied. However, less is known about IRF3 signaling in shaping the adaptive T cell response. To determine the role of IRF3 in the generation and maintenance of effective antiviral T cell responses, mice deficient in IRF3 were infected with a potentially persistent virus, Theiler's murine encephalomyelitis virus (TMEV) or with a model acute infection, influenza A virus (IAV). IRF3 was required to prevent TMEV persistence and induce robust TMEV specific effector T cell responses at the site of infection. This defect was more pronounced in the memory phase with an apparent lack of TMEV-specific memory T cells expressing granzyme B (GrB) in IRF3 deficient mice. In contrast, IRF3 had no effect on antigen specific T cell responses at the effector stage during IAV infection. However, memory T cell responses to IAV were also impaired in IRF3 deficient mice. Furthermore, addition of cytokines during peptide restimulation could not restore GrB expression in IRF3 deficient memory T cells. Taken together, IRF3 plays an important role in the maintenance of effective anti-viral T cell memory responses.

Original languageEnglish (US)
Pages (from-to)426-439
Number of pages14
JournalMicrobes and Infection
Volume17
Issue number6
DOIs
StatePublished - 2015

Fingerprint

Interferon Regulatory Factor-3
Granzymes
Virus Diseases
Maintenance
T-Lymphocytes
Theilovirus
Influenza A virus
Infection
Innate Immunity
Antiviral Agents

Keywords

  • Cytokines
  • Influenza A virus
  • Interferon regulatory factor-3
  • T cell memory
  • T cells
  • Theiler's murine encephalomyelitis virus

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

IRF3 deficiency impacts granzyme B expression and maintenance of memory T cell function in response to viral infection. / Moore, Tyler C.; Vogel, Alexander J.; Petro, Thomas M; Brown, Deborah M.

In: Microbes and Infection, Vol. 17, No. 6, 2015, p. 426-439.

Research output: Contribution to journalArticle

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