The transcription factor nfatp plays a key role in susceptibility to tb in mice

Laura E. Via, Alla V. Tsytsykova, Ricardo Rajsbaum Gorodezky, James V. Falvo, Anne E. Goldfeld

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

In T cells, the transcription factor nuclear factor of activated T cells p (NFATp) is a key regulator of the cytokine genes tumor necrosis factor (TNF) and interferon-γ (IFN-γ). Here, we show that NFATp-deficient (NFATp-/-) mice have a dramatic and highly significant increase in mortality after Mycobacterium tuberculosis (MTb) infection as compared to mortality of control animals after MTb infection. Animals deficient in NFATp have significantly impaired levels of TNF and IFN-γ transcription and protein expression in naïve or total CD4+ T cells, but display wild-type levels of TNF mRNA or protein from MTb-stimulated dendritic cells (DC). The rapid mortality and disease severity observed in MTb-infected NFATp-/- mice is associated with dysregulated production of TNF and IFN-γ in the lungs, as well as with increased levels of TNF, in their serum. Furthermore, global blocking of TNF production by injection of a TNF neutralizaing agent at 6 weeks, but not 12 weeks, post-MTb-infection further decreased the survival rate of both wild-type and NFATp-/- mice, indicating an early role for TNF derived from cells from the monocyte lineage in containment of infection. These results thus demonstrate that NFATp plays a critical role in immune containment of TB disease in vivo, through the NFATp-dependent expression of TNF and IFN-γ in T cells.

Original languageEnglish (US)
Article numbere41427
JournalPLoS One
Volume7
Issue number7
DOIs
StatePublished - Jul 23 2012
Externally publishedYes

Fingerprint

NFATC Transcription Factors
tumor necrosis factors
Transcription Factors
transcription factors
Tumor Necrosis Factor-alpha
T-lymphocytes
mice
Mycobacterium tuberculosis
interferons
Interferons
Mycobacterium Infections
T-cells
Mortality
infection
Animals
TCF Transcription Factors
T-Lymphocytes
Cell Lineage
Transcription
Regulator Genes

ASJC Scopus subject areas

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

Cite this

The transcription factor nfatp plays a key role in susceptibility to tb in mice. / Via, Laura E.; Tsytsykova, Alla V.; Rajsbaum Gorodezky, Ricardo; Falvo, James V.; Goldfeld, Anne E.

In: PLoS One, Vol. 7, No. 7, e41427, 23.07.2012.

Research output: Contribution to journalArticle

Via, Laura E. ; Tsytsykova, Alla V. ; Rajsbaum Gorodezky, Ricardo ; Falvo, James V. ; Goldfeld, Anne E. / The transcription factor nfatp plays a key role in susceptibility to tb in mice. In: PLoS One. 2012 ; Vol. 7, No. 7.
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