Non-human primates: a model for tuberculosis research

Abstract

A variety of animals have been used for tuberculosis research, and each animal model has its strengths and weaknesses. We sought to develop a non-human primate model of tuberculosis to model aspects of human tuberculosis that are difficult to model in other animals, including the pathology in the lungs, various progression to disease, and immunologic correlates of infection or disease that are likely to be similar in humans. To date, we have infected 17 cynomolgus macaques (Macaca fasicularis) with a low dose (15-25CFU) of Mycobacterium tuberculosis strain Erdman. The monkeys were grouped into three categories on the basis of disease progression: rapid progression (advanced disease by 3 months post-infection), active/chronic infection (signs of disease but a slower progression), and latent infection (no signs of clinical disease). Animals were followed clinically post-infection, including blood work, physical examinations, serial bronchoalveolar lavage (BAL) and gastric aspirates for M. tuberculosis culture, chest radiographs, and tuberculin reactivity. Immunologic assays on cells from blood, BAL fluid, and tissue, have been performed, including proliferation, flow cytometry, ELIspot assays, cytotoxic T lymphocyte (CTL) assays, and ELISAs. The spectrum of disease observed in these monkeys is similar to humans, and this model may be very useful for studying pathogenesis and immunology of tuberculosis, as well as testing vaccines, diagnostic reagents, and drugs prior to use in human populations.