The non-human primate model of tuberculosis

Abstract

Non-human primates (NHPs) are used to model human disease owing to their remarkably similar genomes, physiology, and immune systems. Recently, there has been an increased interest in modeling tuberculosis (TB) in NHPs. Macaques are susceptible to infection with different strains of Mycobacterium tuberculosis (Mtb), producing the full spectrum of disease conditions, including latent infection, chronic progressive infection, and acute TB, depending on the route and dose of infection. Clearly, NHPs are an excellent model of human TB. While the initial aim of the NHP model was to allow preclinical testing of candidate vaccines and drugs, it is now also being used to study pathogenesis and immune correlates of protection. Recent advances in this field are discussed in this review. Key questions such as the effect of hypoxia on the biology of Mtb and the basis of reactivation of latent TB can now be investigated through the use of this model.

Fig. 1

Different types of histopathological lesions observed during various Mtb infections of rhesus macaques. A. Centrally caseous lesion with peripheral rim of immune cells is the most typical type of pathology observed in NHPs infected with Mtb. B. A rare fibrotic lesion in a rhesus macaque infected with Mtb. C. Mineralization of a caseous lesion over time in a rhesus macaque infected with Mtb. D. Formation of highly inflamed multinucleated giant macrophages in a lesion from a rhesus macaque infected with Mtb. E. A rare lesion in a rhesus macaque infected with Mtb with a pathology that could be a precursor for cavitation. F. Post-primary lesions in the vicinity of primary, centrally caseous lesions in a rhesus macaque coinfected with Mtb and simian immunodeficiency virus.