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Dominant Negative TRAF3 Variant With Recurrent Mycobacterium abscessus Infection and Bronchiectasis

Mei Fong Liew1, Hui Fang Lim2, Mui Cheng Liang3

  • 1FAST and Chronic Programmes, Alexandra Hospital, National University Health System, Singapore, Singapore.

Open Forum Infectious Diseases
|August 25, 2022
PubMed

Insights

Host factors for pulmonary nontuberculous mycobacteria (PNTM) disease remain unclear. This study identified a tumor necrosis factor receptor associated factor 3 (TRAF3) variant linked to recurrent PNTM infections, revealing TRAF3 and TNF-α deficiencies.

Area of Science:

  • Immunology
  • Genetics
  • Infectious Diseases

Background:

  • Pulmonary nontuberculous mycobacteria (PNTM) disease pathogenesis is poorly understood.
  • Disseminated nontuberculous mycobacteria (NTM) disease is associated with the interleukin-12/interferon-gamma (IL-12/IFN-γ) signaling pathway.
  • Host genetic factors influencing PNTM susceptibility require further investigation.

Purpose of the Study:

  • To investigate the role of the tumor necrosis factor receptor associated factor 3 (TRAF3) R338W variant in a patient with recurrent PNTM infection.
  • To elucidate the impact of this variant on immune function and susceptibility to PNTM.

Main Methods:

  • Genetic analysis of a patient with recurrent PNTM.
  • Ex vivo immune studies to assess cellular responses.
  • Cloning-transfection cellular studies to investigate protein function.

Main Results:

  • Identification of the TRAF3 R338W variant in the patient.
  • Demonstration of TRAF3-deficient and tumor necrosis factor-alpha (TNF-α)-deficient phenotypes.
  • Evidence linking the variant to impaired immune responses.

Conclusions:

  • The TRAF3 R338W variant may contribute to susceptibility to recurrent PNTM disease.
  • TRAF3 and TNF-α signaling are critical for host defense against PNTM.
  • Further research into genetic host factors is warranted for understanding PNTM pathogenesis.
Keywords:
immunocompromised hostnontuberculous mycobacteriapulmonary infectiontransfection

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