Modeling tuberculosis in nonhuman primates

Abstract

Nonhuman primates have emerged as an excellent model of human tuberculosis, in large part because they recapitulate the full spectrum of infection outcome and pathology seen in humans. Several variables inherent to the nonhuman primate models of tuberculosis are discussed in this review, including the monkey species, Mycobacterium tuberculosis strains, and routes of infection, all of which can influence the model to be chosen for various studies. New technologies for studying the microbiology, immunology, and pathogenesis of tuberculosis in nonhuman primates have greatly expanded the capabilities of this model for basic and translational studies, including the development and testing of new treatment and prevention strategies for tuberculosis.

Figure 1.

Pulmonary granuloma from a cynomolgus macaque 20 wk after Mycobacterium tuberculosis infection showing striking similarity to classical TB histopathology in humans. A macrophage-enriched zone (M) surrounds a central area of necrosis (N) with an outer lymphocytic/fibrocytic cuff (L). Original magnification 10×. (Courtesy of Dr. Edwin Klein, University of Pittsburgh.)

Figure 2.

Modeling TB in NHPs facilitates studies based on local responses within individual lesions. Disease can be monitored over time with imaging technologies. Here, serial PET/CT imaging provides the history of a lesion, in terms of size and metabolic activity, over the course of the study. A pre-necropsy scan guides the harvesting of these individual lesions as small as 1 mm that can be portioned out to obtain data on bacterial load, histopathology, immunology, and gene expression. These data are distinct from global immunologic and transcriptional responses (i.e., from PBMC) and can differ from lesion-to-lesion within the same animal. SUV, standardized uptake value; CFU, colony-forming unit. (Figure credit: Chelsea L. Chedrick and Dr. Hannah P. Gideon, University of Pittsburgh.)