{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:57:40Z","timestamp":1790787460269,"version":"4.1.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","award":["TTU-TB 02.814"],"award-info":[{"award-number":["TTU-TB 02.814"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018693","name":"HORIZON EUROPE Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018693","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018855","name":"Imhoff Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018855","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (\n                    <jats:italic>Mtb<\/jats:italic>\n                    ) infection represents a global health problem and is characterized by formation of granuloma with a necrotic center and a systemic inflammatory response. Inflammasomes have a crucial role in the host immune response towards\n                    <jats:italic>Mtb<\/jats:italic>\n                    . These intracellular multi-protein complexes are assembled in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Inflammasome platforms activate caspases, leading to the maturation of the proinflammatory cytokines interleukin (IL)-1 and 18 and the cleavage of gasdermin D (GSDMD), a pore-forming protein responsible for cytokine release and pyroptotic cell death. Recent\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    findings have highlighted the importance of inflammasome signaling and subsequent necrotic cell death in\n                    <jats:italic>Mtb<\/jats:italic>\n                    -infected innate immune cells. However, we are just beginning to understand how inflammasomes contribute to disease or to a protective immune response in tuberculosis (TB). A detailed molecular understanding of inflammasome-associated pathomechanisms may foster the development of novel host-directed therapeutics or vaccines with improved activity. In this mini-review, we discuss the regulatory and molecular aspects of inflammasome activation and the associated immunological consequences for\n                    <jats:italic>Mtb<\/jats:italic>\n                    pathogenesis.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2024.1436676","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:23:31Z","timestamp":1726014211000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["The role of inflammasomes as central inflammatory hubs in Mycobacterium tuberculosis infection"],"prefix":"10.3389","volume":"15","author":[{"given":"Sebastian J.","family":"Theobald","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony A.","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinah","family":"Lange","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Keck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Rybniker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e20","DOI":"10.1016\/S2666-5247(22)00359-7","article-title":"WHO\u2019s global tuberculosis report 2022","volume":"4","author":"Bagcchi","year":"2023","journal-title":"Lancet Microbe"},{"key":"B2","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1007\/s11274-023-03636-x","article-title":"Clinical manifestations and immune response to tuberculosis","volume":"39","author":"Carabali-Isajar","year":"2023","journal-title":"World J Microbiol Biotechnol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2387","article-title":"Evasion of innate immunity by Mycobacterium tuberculosis: is death an exit strategy","volume":"8","author":"Behar","year":"2010","journal-title":"Nat Rev Microbiol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.747799","article-title":"Macrophage: A cell with many faces and functions in tuberculosis","volume":"13","author":"Ahmad","year":"2022","journal-title":"Front Immunol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1016\/j.cell.2016.03.046","article-title":"Inflammasome complexes: emerging mechanisms and effector functions","volume":"165","author":"Rathinam","year":"2016","journal-title":"Cell"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.58","article-title":"Inflammasomes: mechanism of assembly, regulation and signalling","volume":"16","author":"Broz","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00599-3","article-title":"The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta","volume":"10","author":"Martinon","year":"2002","journal-title":"Mol Cell"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nature10394","article-title":"Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity","volume":"477","author":"Kofoed","year":"2011","journal-title":"Nature"},{"key":"B9","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1038\/nature10510","article-title":"The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus","volume":"477","author":"Zhao","year":"2011","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nature07725","article-title":"AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC","volume":"458","author":"Hornung","year":"2009","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nature07710","article-title":"AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA","volume":"458","author":"Fernandes-Alnemri","year":"2009","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0165-0","article-title":"The NLRP3 inflammasome: molecular activation and regulation to therapeutics","volume":"19","author":"Swanson","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"3328","DOI":"10.3390\/ijms20133328","article-title":"The NLRP3 inflammasome: an overview of mechanisms of activation and regulation","volume":"20","author":"Kelley","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B14","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/nri3452","article-title":"Activation and regulation of the inflammasomes","volume":"13","author":"Latz","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2010.01450.x","article-title":"Mycobacterium tuberculosis protein ESAT-6 is a potent activator of the NLRP3\/ASC inflammasome","volume":"12","author":"Mishra","year":"2010","journal-title":"Cell Microbiol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2011.01625.x","article-title":"Critical role for NLRP3 in necrotic death triggered by Mycobacterium tuberculosis","volume":"13","author":"Wong","year":"2011","journal-title":"Cell Microbiol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/s41420-021-00716-5","article-title":"Gasdermin D mediates host cell death but not interleukin-1beta secretion in Mycobacterium tuberculosis-infected macrophages","volume":"7","author":"Theobald","year":"2021","journal-title":"Cell Death Discovery"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01427","article-title":"Lysosomal cathepsin release is required for NLRP3-inflammasome activation by mycobacterium tuberculosis in infected macrophages","volume":"9","author":"Amaral","year":"2018","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201141548","article-title":"Activation of the NLRP3 inflammasome by Mycobacterium tuberculosis is uncoupled from susceptibility to active tuberculosis","volume":"42","author":"Dorhoi","year":"2012","journal-title":"Eur J Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2017.11.044","article-title":"NLRP3 inflammasome activation by mycobacterial ESAT-6 and dsRNA in intraocular tuberculosis","volume":"114","author":"Basu","year":"2018","journal-title":"Microb Pathog"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22448","article-title":"Microglial activation of the NLRP3 inflammasome by the priming signals derived from macrophages infected with mycobacteria","volume":"61","author":"Lee","year":"2013","journal-title":"Glia"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2270","DOI":"10.1038\/s41467-020-16143-6","article-title":"Plasma membrane damage causes NLRP3 activation and pyroptosis during Mycobacterium tuberculosis infection","volume":"11","author":"Beckwith","year":"2020","journal-title":"Nat Commun"},{"key":"B23","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/j.chembiol.2023.12.007","article-title":"Discovery of dual-active ethionamide boosters inhibiting the Mycobacterium tuberculosis ESX-1 secretion system","volume":"31","author":"Gries","year":"2024","journal-title":"Cell Chem Biol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba4733","article-title":"Mycobacterial EST12 activates a RACK1-NLRP3-gasdermin D pyroptosis-IL-1beta immune pathway","volume":"6","author":"Qu","year":"2020","journal-title":"Sci Adv"},{"key":"B25","doi-asserted-by":"publisher","first-page":"eabq0132","DOI":"10.1126\/science.abq0132","article-title":"A bacterial phospholipid phosphatase inhibits host pyroptosis by hijacking ubiquitin","volume":"378","author":"Chai","year":"2022","journal-title":"Science"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e1009712","DOI":"10.1371\/journal.ppat.1009712","article-title":"Mycobacterium tuberculosis inhibits the NLRP3 inflammasome activation via its phosphokinase PknF","volume":"17","author":"Rastogi","year":"2021","journal-title":"PloS Pathog"},{"key":"B27","doi-asserted-by":"publisher","first-page":"127547","DOI":"10.1016\/j.ijbiomac.2023.127547","article-title":"PE12 interaction with TLR4 promotes intracellular survival of Mycobacterium tuberculosis by suppressing inflammatory response","volume":"253","author":"Zhang","year":"2023","journal-title":"Int J Biol Macromol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e12320","DOI":"10.1371\/journal.pone.0012320","article-title":"Granuloma formation and host defense in chronic Mycobacterium tuberculosis infection requires PYCARD\/ASC but not NLRP3 or caspase-1","volume":"5","author":"McElvania Tekippe","year":"2010","journal-title":"PloS One"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0904189","article-title":"Caspase-1 independent IL-1beta production is critical for host resistance to mycobacterium tuberculosis and does not require TLR signaling in vivo","volume":"184","author":"Mayer-Barber","year":"2010","journal-title":"J Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e0006023","DOI":"10.1128\/iai.00060-23","article-title":"High lethality of mycobacterium tuberculosis infection in mice lacking the phagocyte oxidase and caspase1\/11","volume":"91","author":"Thomas","year":"2023","journal-title":"Infect Immun"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1758","DOI":"10.1016\/j.immuni.2021.06.009","article-title":"Macrophage and neutrophil death programs differentially confer resistance to tuberculosis","volume":"54","author":"Stutz","year":"2021","journal-title":"Immunity"},{"key":"B32","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1038\/s41467-022-28506-2","article-title":"Early alveolar macrophage response and IL-1R-dependent T cell priming determine transmissibility of Mycobacterium tuberculosis strains","volume":"13","author":"Lovey","year":"2022","journal-title":"Nat Commun"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.12.002","article-title":"Innate and adaptive interferons suppress IL-1alpha and IL-1beta production by distinct pulmonary myeloid subsets during Mycobacterium tuberculosis infection","volume":"35","author":"Mayer-Barber","year":"2011","journal-title":"Immunity"},{"key":"B34","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/nature13489","article-title":"Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk","volume":"511","author":"Mayer-Barber","year":"2014","journal-title":"Nature"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxs062","article-title":"Critical role of AIM2 in Mycobacterium tuberculosis infection","volume":"24","author":"Saiga","year":"2012","journal-title":"Int Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit347","article-title":"the AIM2 inflammasome is involved in macrophage activation during infection with virulent Mycobacterium bovis strain","volume":"208","author":"Yang","year":"2013","journal-title":"J Infect Dis"},{"key":"B37","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/j.chom.2015.05.003","article-title":"Mycobacterium tuberculosis Differentially Activates cGAS- and Inflammasome-Dependent Intracellular Immune Responses through ESX-1","volume":"17","author":"Wassermann","year":"2015","journal-title":"Cell Host Microbe"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701177","article-title":"Deficiency of the AIM2-ASC signal uncovers the STING-driven overreactive response of type I IFN and reciprocal depression of protective IFN-gamma immunity in mycobacterial infection","volume":"200","author":"Yan","year":"2018","journal-title":"J Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301331","article-title":"Cutting edge: Mycobacterium tuberculosis but not nonvirulent mycobacteria inhibits IFN-beta and AIM2 inflammasome-dependent IL-1beta production via its ESX-1 secretion system","volume":"191","author":"Shah","year":"2013","journal-title":"J Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2300418","article-title":"Cutting Edge: Cytosolic Receptor AIM2 Is Induced by Peroxisome Proliferator-activated Receptor gamma following Mycobacterium tuberculosis Infection of Human Macrophages but Does Not Contribute to IL-1beta Release","volume":"212","author":"Arnett","year":"2024","journal-title":"J Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"3709","DOI":"10.1038\/s41598-020-60560-y","article-title":"Genetic and pharmacological inhibition of inflammasomes reduces the survival of Mycobacterium tuberculosis strains in macrophages","volume":"10","author":"Subbarao","year":"2020","journal-title":"Sci Rep"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.550624","article-title":"Combining host genetics and functional analysis to depict inflammasome contribution in tuberculosis susceptibility and outcome in endemic areas","volume":"11","author":"Souza De Lima","year":"2020","journal-title":"Front Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2016.04.015","article-title":"Inflammasome genetics contributes to the development and control of active pulmonary tuberculosis","volume":"41","author":"Souza de Lima","year":"2016","journal-title":"Infect Genet Evol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502203","article-title":"Aberrant inflammasome activation characterizes tuberculosis-associated immune reconstitution inflammatory syndrome","volume":"196","author":"Tan","year":"2016","journal-title":"J Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180325","article-title":"Type I interferons in tuberculosis: Foe and occasionally friend","volume":"215","author":"Moreira-Teixeira","year":"2018","journal-title":"J Exp Med"},{"key":"B46","doi-asserted-by":"publisher","first-page":"175091","DOI":"10.1016\/j.ejphar.2022.175091","article-title":"Therapeutic potential of MCC950, a specific inhibitor of NLRP3 inflammasome","volume":"928","author":"Li","year":"2022","journal-title":"Eur J Pharmacol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1038\/nrd.2018.149","article-title":"Targeting the NLRP3 inflammasome in inflammatory diseases","volume":"17","author":"Mangan","year":"2018","journal-title":"Nat Rev Drug Discovery"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1436676\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:23:36Z","timestamp":1726014216000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1436676\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,11]]},"references-count":47,"alternative-id":["10.3389\/fimmu.2024.1436676"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1436676","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,11]]},"article-number":"1436676"}}