An aerosol challenge model of tuberculosis in Mauritian cynomolgus macaques

PLoS One. 2017 Mar 8;12(3):e0171906. doi: 10.1371/journal.pone.0171906. eCollection 2017.

Abstract

Background: New interventions for tuberculosis are urgently needed. Non-human primate (NHP) models provide the most relevant pre-clinical models of human disease and play a critical role in vaccine development. Models utilising Asian cynomolgus macaque populations are well established but the restricted genetic diversity of the Mauritian cynomolgus macaques may be of added value.

Methods: Mauritian cynomolgus macaques were exposed to a range of doses of M. tuberculosis delivered by aerosol, and the outcome was assessed using clinical, imaging and pathology-based measures.

Results: All macaques developed characteristic clinical signs and disease features of tuberculosis (TB). Disease burden and the ability to control disease were dependent on exposure dose. Mauritian cynomolgus macaques showed less variation in pulmonary disease burden and total gross pathology scores within exposure dose groups than either Indian rhesus macaques or Chinese cynomolgus macaques.

Conclusions: The genetic homogeneity of Mauritian cynomolgus macaques makes them a potentially useful model of human tuberculosis.

MeSH terms

  • Animals
  • Enzyme-Linked Immunospot Assay
  • Interferon-gamma / blood
  • Interferon-gamma / metabolism
  • Kidney / pathology
  • Liver / pathology
  • Lung / diagnostic imaging
  • Lung / microbiology
  • Lung / pathology
  • Macaca fascicularis / immunology
  • Macaca fascicularis / microbiology*
  • Magnetic Resonance Imaging
  • Mycobacterium tuberculosis / physiology*
  • Radiography, Thoracic
  • Severity of Illness Index
  • Tuberculosis / pathology*

Substances

  • Interferon-gamma