{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:56:58Z","timestamp":1793051818940,"version":"4.5.0"},"reference-count":326,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Despite years of global efforts to combat tuberculosis (TB), <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>Mtb<\/jats:italic>), the causative agent of this disease, continues to haunt the humankind making TB elimination a distant task. To comprehend the pathogenic nuances of this organism, various <jats:italic>in vitro, ex vivo<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> experimental models have been employed by researchers. This review focuses on the salient features as well as pros and cons of various model systems employed for TB research. <jats:italic>In vitro<\/jats:italic> and <jats:italic>ex vivo<\/jats:italic> macrophage infection models have been extensively used for studying <jats:italic>Mtb<\/jats:italic> physiology. Animal models have provided us with great wealth of information and have immensely contributed to the understanding of TB pathogenesis and host responses during infection. Additionally, they have been used for evaluation of anti-mycobacterial drug therapy as well as for determining the efficacy of potential vaccine candidates. Advancements in various \u2018omics\u2019 based approaches have enhanced our understanding about the host-pathogen interface. Although animal models have been the cornerstone to TB research, none of them is ideal that gives us a complete picture of human infection, disease and progression. Further, the review also discusses about the newer systems including three dimensional (3D)-tissue models, lung-on-chip infection model, <jats:italic>in vitro<\/jats:italic> TB granuloma model and their limitations for studying TB. Thus, converging information gained from various <jats:italic>in vitro<\/jats:italic> and <jats:italic>ex vivo<\/jats:italic> models in tandem with <jats:italic>in vivo<\/jats:italic> experiments will ultimately bridge the gap that exists in understanding human TB.<\/jats:p>","DOI":"10.3389\/fcimb.2025.1572547","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T05:25:36Z","timestamp":1746681936000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Model systems to study Mycobacterium tuberculosis infections: an overview of scientific potential and impediments"],"prefix":"10.3389","volume":"15","author":[{"given":"Prachi","family":"Nangpal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha Lalwani","family":"Nagpal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nupur","family":"Angrish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garima","family":"Khare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3155","DOI":"10.4049\/jimmunol.169.6.3155","article-title":"Toll-like receptor 4 expression is required to control chronic Mycobacterium tuberculosis infection in mice","volume":"169","author":"Abel","year":"2002","journal-title":"J. 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