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Sci Rep. 2017 Sep 5;7(1):10496. doi: 10.1038/s41598-017-10980-0.

T-bet, but not Gata3, overexpression is detrimental in a neurotropic viral infection.

Sato F1,2,3,4, Kawai E2,3, Martinez NE2,3, Omura S1,2,3,4, Park AM1, Takahashi S5,6,7,8, Yoh K5, Tsunoda I9,10,11,12.

Author information

1
Department of Microbiology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511, Japan.
2
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center-Shreveport (LSUHSC-S), 1501 Kings Highway, Shreveport, LA 71130, USA.
3
Center for Molecular and Tumor Virology (CMTV), Louisiana State University Health Sciences Center-Shreveport (LSUHSC-S), 1501 Kings Highway, Shreveport, LA 71130, USA.
4
Center for Cardiovascular Diseases and Sciences (CCDS), Louisiana State University Health Sciences Center-Shreveport (LSUHSC-S), 1501 Kings Highway, Shreveport, LA 71130, USA.
5
Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
6
International Institute for Investigative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
7
Life Science Center, Tsukuba Research Alliance (TARA), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
8
Laboratory Animal Resource Center (LARC), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
9
Department of Microbiology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511, Japan. itsunoda@med.kindai.ac.jp.
10
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center-Shreveport (LSUHSC-S), 1501 Kings Highway, Shreveport, LA 71130, USA. itsunoda@med.kindai.ac.jp.
11
Center for Molecular and Tumor Virology (CMTV), Louisiana State University Health Sciences Center-Shreveport (LSUHSC-S), 1501 Kings Highway, Shreveport, LA 71130, USA. itsunoda@med.kindai.ac.jp.
12
Center for Cardiovascular Diseases and Sciences (CCDS), Louisiana State University Health Sciences Center-Shreveport (LSUHSC-S), 1501 Kings Highway, Shreveport, LA 71130, USA. itsunoda@med.kindai.ac.jp.

Abstract

Intracerebral Theiler's murine encephalomyelitis virus (TMEV) infection in mice induces inflammatory demyelination in the central nervous system. Although C57BL/6 mice normally resistant to TMEV infection with viral clearance, we have previously demonstrated that RORγt-transgenic (tg) C57BL/6 mice, which have Th17-biased responses due to RORγt overexpression in T cells, became susceptible to TMEV infection with viral persistence. Here, using T-bet-tg C57BL/6 mice and Gata3-tg C57BL/6 mice, we demonstrated that overexpression of T-bet, but not Gata3, in T cells was detrimental in TMEV infection. Unexpectedly, T-bet-tg mice died 2 to 3 weeks after infection due to failure of viral clearance. Here, TMEV infection induced splenic T cell depletion, which was associated with lower anti-viral antibody and T cell responses. In contrast, Gata3-tg mice remained resistant, while Gata3-tg mice had lower IFN-γ and higher IL-4 production with increased anti-viral IgG1 responses. Thus, our data identify how overexpression of T-bet and Gata3 in T cells alters anti-viral immunity and confers susceptibility to TMEV infection.

PMID:
28874814
PMCID:
PMC5585213
DOI:
10.1038/s41598-017-10980-0
[Indexed for MEDLINE]
Free PMC Article

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