{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:38:49Z","timestamp":1792600729424,"version":"4.5.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tuberculosis (TB) granulomas are complex multicellular structures central to disease pathogenesis and treatment challenges, notably due to bacterial persistence and immune modulation. Existing animal and in vitro models do not fully capture granuloma heterogeneity and immune complexity. Here, we review the biology and applications of Granuloma-Like Structures (GLS) derived from human peripheral blood mononuclear cells infected with Mycobacterium tuberculosis, which recapitulate key features of early granuloma formation, including macrophage differentiation, lymphocyte involvement, and cytokine dynamics. Quantitative analysis identifies conserved bacterial growth trajectories and recurrent aggregate sizes, despite protocol diversity and donor variability. Furthermore, a minimal theoretical model illustrates how aggregate size may influence drug efficacy, through physical and biological mechanisms. Although underutilized in drug screening, GLS offer a promising intermediate platform by bridging simple cell monolayers to animal models, particularly for evaluating host-directed therapies. Standardized metrics and integration with computational models are needed to enhance reproducibility and translational relevance. GLS thus represent a valuable tool to investigate host\u2013pathogen interactions and advance TB drug development under controlled immune conditions.<\/jats:p>","DOI":"10.1093\/femsre\/fuag053","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T11:47:29Z","timestamp":1792583249000},"source":"Crossref","is-referenced-by-count":0,"title":["Granuloma-Like Structures in Tuberculosis A Critical Review of Their Biology, Quantitative Behavior, and Translational Use"],"prefix":"10.1093","author":[{"given":"Enrico","family":"Mastrostefano","sequence":"first","affiliation":[{"name":"Istituto per le Applicazioni del Calcolo \u201cMauro Picone\u201d , IAC \u2013 Consiglio Nazionale delle Ricerche, Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Delogu","sequence":"additional","affiliation":[{"name":"University of Parma Department of Medicine and Surgery, , Parma ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Stamilla","sequence":"additional","affiliation":[{"name":"University of Pavia Department of Biology and Biotechnology \u201cLazzaro Spallanzani\u201d, , Pavia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Segafreddo","sequence":"additional","affiliation":[{"name":"University of Padua Department of Molecular Medicine, , Padua ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Palucci","sequence":"additional","affiliation":[{"name":"Intensivological and Perioperative Clinics Department of Basic Biotechnological Sciences, , Universit\u00e0 Cattolica del Sacro Cuore, Rome ,","place":["Italy"]},{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS Department of Laboratory and Hematological Sciences, , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Degiacomi","sequence":"additional","affiliation":[{"name":"University of Pavia Department of Biology and Biotechnology \u201cLazzaro Spallanzani\u201d, , Pavia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Boldrin","sequence":"additional","affiliation":[{"name":"University of Padua Department of Molecular Medicine, , Padua ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Ravoni","sequence":"additional","affiliation":[{"name":"Istituto per le Applicazioni del Calcolo \u201cMauro Picone\u201d , IAC \u2013 Consiglio Nazionale delle Ricerche, Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Moretti","sequence":"additional","affiliation":[{"name":"Istituto per le Applicazioni del Calcolo \u201cMauro Picone\u201d , IAC \u2013 Consiglio Nazionale delle Ricerche, Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8391-2563","authenticated-orcid":false,"given":"Elia","family":"Onofri","sequence":"additional","affiliation":[{"name":"Istituto per le Applicazioni del Calcolo \u201cMauro Picone\u201d , IAC \u2013 Consiglio Nazionale delle Ricerche, Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Dal","family":"Molin","sequence":"additional","affiliation":[{"name":"University of Cologne Department I of Internal Medicine, , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Rybniker","sequence":"additional","affiliation":[{"name":"University of Cologne Department I of Internal Medicine, , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Sorze","sequence":"additional","affiliation":[{"name":"University of Padua Department of Molecular Medicine, , Padua ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica","family":"Campagnaro","sequence":"additional","affiliation":[{"name":"University of Padua Department of Molecular Medicine, , Padua ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Cioetto-Mazzabo","sequence":"additional","affiliation":[{"name":"University of Padua Department of Molecular Medicine, , Padua ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Tieri","sequence":"additional","affiliation":[{"name":"Istituto per le Applicazioni del Calcolo \u201cMauro Picone\u201d , IAC \u2013 Consiglio Nazionale delle Ricerche, Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Ram\u00f3n-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Pediatrics, Radiology and Public Health, Faculty of Medicine, University of Zaragoza Department of Microbiology, , Zaragoza ,","place":["Spain"]},{"name":"Research & Development Agency of Arag\u00f3n Foundation (Fundaci\u00f3n ARAID) , Zaragoza ,","place":["Spain"]},{"name":"Spanish Network for Research on Respiratory Diseases (CIBERES), Carlos III Health Institute , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosalia","family":"Pasca","sequence":"additional","affiliation":[{"name":"University of Pavia Department of Biology and Biotechnology \u201cLazzaro Spallanzani\u201d, , Pavia ,","place":["Italy"]},{"name":"Fondazione IRCCS Policlinico San Matteo , Pavia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0940-7336","authenticated-orcid":false,"given":"Riccardo","family":"Manganelli","sequence":"additional","affiliation":[{"name":"University of Padua Department of Molecular Medicine, , Padua ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,21]]},"container-title":["FEMS Microbiology Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/femsre\/advance-article-pdf\/doi\/10.1093\/femsre\/fuag053\/72256833\/fuag053.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/femsre\/advance-article-pdf\/doi\/10.1093\/femsre\/fuag053\/72256833\/fuag053.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:44:46Z","timestamp":1792597486000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/femsre\/advance-article\/doi\/10.1093\/femsre\/fuag053\/8965145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,21]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/femsre\/fuag053","relation":{},"ISSN":["0168-6445","1574-6976"],"issn-type":[{"value":"0168-6445","type":"print"},{"value":"1574-6976","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,21]]},"article-number":"fuag053"}}