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With the development of more complex<jats:italic>in vitro<\/jats:italic>models, there is a need for tools to help analyze and integrate data from these models. To this end, we introduce an agent-based model (ABM) representation of the interactions between immune cells and bacteria in an<jats:italic>in vitro<\/jats:italic>setting. This<jats:italic>in silico<\/jats:italic>model was used to simulate both traditional and spheroid cell culture models by changing the movement rules and initial spatial layout of the cells in accordance with the respective<jats:italic>in vitro<\/jats:italic>models. The traditional and spheroid simulations were calibrated to published experimental data in a paired manner, by using the same parameters in both simulations. Within the calibrated simulations, heterogeneous outputs are seen for bacterial count and T cell infiltration into the macrophage core of the spheroid. The simulations also predict that equivalent numbers of activated macrophages do not necessarily result in similar bacterial reductions; that host immune responses can control bacterial growth in both spheroid structure dependent and independent manners; that STAT1 activation is the limiting step in macrophage activation in spheroids; and that drug screening and macrophage activation studies could have different outcomes depending on the<jats:italic>in vitro<\/jats:italic>culture used. Future model iterations will be guided by the limitations of the current model, specifically which parts of the output space were harder to reach. This ABM can be used to represent more<jats:italic>in vitro Mtb<\/jats:italic>infection models due to its flexible structure, thereby accelerating<jats:italic>in vitro<\/jats:italic>discoveries.<\/jats:p>","DOI":"10.1371\/journal.pone.0299107","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T17:39:07Z","timestamp":1711129147000},"page":"e0299107","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["In silico agent-based modeling approach to characterize multiple in vitro tuberculosis infection models"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8294-6155","authenticated-orcid":true,"given":"Alexa","family":"Petrucciani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexis","family":"Hoerter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2019-8777","authenticated-orcid":true,"given":"Leigh","family":"Kotze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelita","family":"Du Plessis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5408-8795","authenticated-orcid":true,"given":"Elsje","family":"Pienaar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,3,22]]},"reference":[{"key":"pone.0299107.ref001","author":"World Health Organization","year":"2022","journal-title":"Global Tuberculosis Report"},{"key":"pone.0299107.ref002","first-page":"9","article-title":"The Immune Mechanisms of Lung Parenchymal Damage in Tuberculosis and the Role of Host-Directed Therapy.","author":"C Stek","year":"2018","journal-title":"Front Microbiol"},{"key":"pone.0299107.ref003","doi-asserted-by":"crossref","first-page":"5071","DOI":"10.1096\/fj.14-255786","article-title":"Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes","volume":"28","author":"BJ Edagwa","year":"2014","journal-title":"FASEB J"},{"key":"pone.0299107.ref004","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1128\/IAI.00906-12","article-title":"Mycobacterial Trehalose Dimycolate Reprograms Macrophage Global Gene Expression and Activates Matrix Metalloproteinases.","volume":"81","author":"K Sakamoto","year":"2013","journal-title":"Infect Immun"},{"key":"pone.0299107.ref005","doi-asserted-by":"crossref","first-page":"e12266","DOI":"10.1371\/journal.pone.0012266","article-title":"Transcriptional Reprogramming in Nonhuman Primate (Rhesus Macaque) Tuberculosis Granulomas.","volume":"5","author":"S Mehra","year":"2010","journal-title":"PLoS One."},{"key":"pone.0299107.ref006","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s00281-015-0534-0","article-title":"Immunometabolism within the tuberculosis granuloma: amino acids, hypoxia, and cellular respiration.","volume":"38","author":"JE Qualls","year":"2016","journal-title":"Semin Immunopathol."},{"key":"pone.0299107.ref007","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/cshperspect.a018499","article-title":"Immunity and immunopathology in the tuberculous granuloma","volume":"5","author":"AJ Pag\u00e1n","year":"2015","journal-title":"Cold Spring Harb Perspect Med"},{"key":"pone.0299107.ref008","doi-asserted-by":"crossref","first-page":"613149","DOI":"10.3389\/fcimb.2021.613149","article-title":"One Size Fits All? 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