Comparative pathology of experimental pulmonary tuberculosis in animal models

Abstract

Research in human tuberculosis (TB) is limited by the availability of human tissues from patients, which is often altered by therapy and treatment. Thus, the use of animal models is a key tool in increasing our understanding of the pathogenesis, disease progression and preclinical evaluation of new therapies and vaccines. The granuloma is the hallmark lesion of pulmonary tuberculosis, regardless of the species or animal model used. Although animal models may not fully replicate all the histopathological characteristics observed in natural, human TB disease, each one brings its own attributes which enable researchers to answer specific questions regarding TB immunopathogenesis. This review delves into the pulmonary pathology induced by Mycobacterium tuberculosis complex (MTBC) bacteria in different animal models (non-human primates, rodents, guinea pigs, rabbits, cattle, goats, and others) and compares how they relate to the pulmonary disease described in humans. Although the described models have demonstrated some histopathological features in common with human pulmonary TB, these data should be considered carefully in the context of this disease. Further research is necessary to establish the most appropriate model for the study of TB, and to carry out a standard characterisation and score of pulmonary lesions.

Effect of IL-17A on the immune response to pulmonary tuberculosis induced by high- and low-virulence strains of Mycobacterium bovis

“…Research in human TB is limited due to the difficulty to get samples of the injured lung tissue, and the immune response, pathogenic characteristics and severity is related to the clinical phase of this chronic disease that is also affected by the therapy and social conditions of the patients [ 95 , 96 ]. Thus, diverse animal models have been created and they substantially contributed to the understanding of the pathogenesis, disease progression and preclinical evaluation of new therapies and vaccines [ 23 ]. Relevant models in non-human primates, guinea pigs, rabbits, ruminants, and rodents, among others have been established [ 17 , 22 , 23 , 97 , 98 ].…”

“…Thus, diverse animal models have been created and they substantially contributed to the understanding of the pathogenesis, disease progression and preclinical evaluation of new therapies and vaccines [ 23 ]. Relevant models in non-human primates, guinea pigs, rabbits, ruminants, and rodents, among others have been established [ 17 , 22 , 23 , 97 , 98 ]. Each one of these models has its own attributes that have permitted the study of diverse aspects of TB immunopathogenesis.…”

“…To study the interaction between the immune response and mycobacteria in the lungs, several animal models are used [ 17 ], such as guinea pigs [ 18 ], rabbits [ 19 ], monkeys [ 20 ], and mice, with murine models being the most common [ 21 , 22 ]. Although experimental murine TB cannot totally imitate human TB due to diverse factors and complexities, these models have provided valuable insights into TB pathogenesis and treatment [ 12 , 23 ]. Some mouse models have been developed to characterize the cellular and molecular processes involved in bovine TB immunopathogenesis and the formation of necrotic granulomas [ 15 , 24 ].…”

Immunopathology of Pulmonary Mycobacterium tuberculosis Infection in a Humanized Mouse Model

“…Several animal models of Mtb infection have been utilized to explore the host-pathogen interactions underlying active TB and LTBI with variable levels of success in reproducing the pathophysiology of respective conditions in humans [8,9]. For example, pathogenic Mtb infection can produce caseous necrotic granulomas that undergo cavitation in non-human primate (NHP) and rabbit models [10,11].…”