期刊
SEMINARS IN IMMUNOPATHOLOGY
卷 38, 期 2, 页码 221-237出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00281-015-0538-9
关键词
Tuberculosis; Granuloma; Necrosis; Animal models; Inbred mice; Mechanisms; Host-directed therapies; sst1
资金
- NHLBI NIH HHS [R01 HL126066, R01 HL059836] Funding Source: Medline
- NIAID NIH HHS [R33 AI105944] Funding Source: Medline
A key aspect of TB pathogenesis that maintains Mycobacterium tuberculosis in the human population is the ability to cause necrosis in pulmonary lesions. As co-evolution shaped M . tuberculosis (M.tb) and human responses, the complete TB disease profile and lesion manifestation are not fully reproduced by any animal model. However, animal models are absolutely critical to understand how infection with virulent M.tb generates outcomes necessary for the pathogen transmission and evolutionary success. In humans, a wide spectrum of TB outcomes has been recognized based on clinical and epidemiological data. In mice, there is clear genetic basis for susceptibility. Although the spectra of human and mouse TB do not completely overlap, comparison of human TB with mouse lesions across genetically diverse strains firmly establishes points of convergence. By embracing the genetic heterogeneity of the mouse population, we gain tremendous advantage in the quest for suitable in vivo models. Below, we review genetically defined mouse models that recapitulate a key element of M.tb pathogenesis-induction of necrotic TB lesions in the lungs-and discuss how these models may reflect TB stratification and pathogenesis in humans. The approach ensures that roles that mouse models play in basic and translational TB research will continue to increase allowing researchers to address fundamental questions of TB pathogenesis and bacterial physiology in vivo using this well-defined, reproducible, and cost-efficient system. Combination of the new generation mouse models with advanced imaging technologies will also allow rapid and inexpensive assessment of experimental vaccines and therapies prior to testing in larger animals and clinical trials.
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