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The transcription factor NFATp plays a key role in susceptibility to TB in mice

Laura E Via1, Alla V Tsytsykova, Ricardo Rajsbaum

  • 1Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, United States of America.

Plos One
|July 31, 2012
PubMed

Insights

Nuclear factor of activated T cells p (NFATp) is crucial for controlling Mycobacterium tuberculosis (MTb) infection. NFATp deficiency in mice leads to increased mortality and impaired T cell cytokine production, highlighting NFATp

Area of Science:

  • Immunology
  • Molecular Biology
  • Infectious Diseases

Background:

  • Nuclear factor of activated T cells p (NFATp) regulates key cytokine genes like tumor necrosis factor (TNF) and interferon-gamma (IFN-γ) in T cells.
  • T cell-derived cytokines are critical for controlling intracellular pathogens such as Mycobacterium tuberculosis (MTb).

Purpose of the Study:

  • To investigate the role of NFATp in the immune response to Mycobacterium tuberculosis (MTb) infection in vivo.
  • To determine the impact of NFATp deficiency on T cell cytokine production and host survival during MTb infection.

Main Methods:

  • Utilized NFATp-deficient (NFATp(-/-)) and wild-type mice models for Mycobacterium tuberculosis (MTb) infection studies.
  • Assessed mortality rates, cytokine (TNF and IFN-γ) transcription and protein expression in T cells and dendritic cells (DCs), and serum cytokine levels.
  • Administered TNF-neutralizing agents at different time points post-infection to evaluate the role of TNF in infection containment.

Main Results:

  • NFATp(-/-) mice exhibited significantly increased mortality and disease severity following MTb infection compared to control animals.
  • T cells from NFATp(-/-) mice showed impaired transcription and expression of TNF and IFN-γ.
  • Dysregulated TNF and IFN-γ production in the lungs and elevated serum TNF levels were observed in infected NFATp(-/-) mice.
  • Early but not late blockade of TNF further reduced survival, indicating an early role for TNF in infection control.

Conclusions:

  • NFATp plays a critical role in the in vivo immune containment of tuberculosis (TB) disease.
  • NFATp-dependent expression of TNF and IFN-γ in T cells is essential for controlling MTb infection.
  • These findings underscore the importance of NFATp in orchestrating an effective T cell-mediated immune response against TB.

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