PPD-induced monocyte mitochondrial damage is associated with a protective effect to develop tuberculosis in BCG

Diana Marín1,2, Nancy Marín2,3, Helena Del Corral1,2

  • 1Grupo de Epidemiología, Facultad Nacional de Salud Pública, Universidad de Antioquia, Medellín, Colombia.

Plos One
|February 22, 2017
PubMed
Abstract

Insights

Monocyte mitochondrial damage induced by purified protein derivative (PPD) stimulation correlates with protection against tuberculosis (TB) disease in BCG-vaccinated individuals. This finding may help predict TB susceptibility in household contacts.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Public Health

Background:

  • Mechanisms of mononuclear phagocyte death are linked to mycobacterial replication.
  • The predictive value of these mechanisms for tuberculosis (TB) risk remains unclear.

Purpose of the Study:

  • To identify factors associated with monocyte mitochondrial and membrane damage induced by purified protein derivative (PPD).
  • To determine if this monocyte damage predicts susceptibility to active TB in household contacts (HHCs).

Main Methods:

  • Prospective cohort study of 2060 HHCs of TB patients followed for two years.
  • Mononuclear cell cultures stimulated with PPD; monocyte death assessed by flow cytometry.
  • Logistic regression and survival analysis (Kaplan-Meier, Cox regression) used.

Main Results:

  • Monocyte death observed in 1,859/2,060 HHCs.
  • PPD stimulation induced mitochondrial damage in 83.4% and membrane damage in 50.9%.
  • Mitochondrial damage in BCG-vaccinated HHCs was associated with a significantly reduced risk of developing active TB (HR = 0.19).

Conclusions:

  • PPD-induced monocyte mitochondrial damage correlates with protection against TB development in BCG-vaccinated HHCs.
  • This cellular damage mechanism could serve as a predictive tool for TB susceptibility in high-risk populations.

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