{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T04:22:35Z","timestamp":1778041355587,"version":"3.51.4"},"reference-count":52,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,12,27]],"date-time":"2012-12-27T00:00:00Z","timestamp":1356566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The inflammasome is a multimolecular complex that orchestrates the activation of proinflammatory caspases and interleukin (IL)\u20101\u03b2, which is generally increased in the cerebrospinal fluids of patients with tuberculous meningitis. However, it has not been clarified whether mycobacteria can activate the inflammasome and induce IL\u20101\u03b2 maturation in microglia. In this study, we found that the priming of primary murine microglial cells with conditioned media from cultures of macrophages infected with <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (Mtb) led to robust activation of caspase\u20101 and IL\u20101\u03b2 secretion after Mtb stimulation. Potassium efflux and the lysosomal proteases cathepsin B and cathepsin L were required for the Mtb\u2010induced caspase\u20101 activation and maturation of IL\u20101\u03b2 production in primed microglia. Mtb\u2010induced IL\u20101\u03b2 maturation was also found to depend on the nucleotide binding and oligomerization of domain\u2010like receptor family pyrin domain containing 3 protein (NLRP3) and apoptosis\u2010associated speck\u2010like protein containing a caspase recruitment domain (ASC), as well as the generation of mitochondrial reactive oxygen species (ROS). Notably, the priming of microglia with tumor necrosis factor\u2010\u03b1 or oncostatin M resulted in caspase\u20101 cleavage and IL\u20101\u03b2 secretion in response to Mtb. Moreover, dexamethasone, as an adjunctive therapy for patients of tuberculous meningitis, significantly reduced the Mtb\u2010induced maturation of IL\u20101\u03b2 through inhibition of mitochondrial ROS generation. Collectively, these data suggest that Mtb stimulation induces activation of the microglial NLRP3 inflammasome (composed of NLRP3, ASC, and cysteine protease caspase\u20101) through microglia\u2013leukocyte interactions as a priming signal, and that dexamethasone decreases inflammasome activation through inhibition of ROS of mitochondrial origin. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/glia.22448","type":"journal-article","created":{"date-parts":[[2012,12,28]],"date-time":"2012-12-28T04:45:07Z","timestamp":1356669907000},"page":"441-452","source":"Crossref","is-referenced-by-count":55,"title":["Microglial activation of the NLRP3 inflammasome by the priming signals derived from macrophages infected with mycobacteria"],"prefix":"10.1002","volume":"61","author":[{"given":"Hye\u2010Mi","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junghee","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Joong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun\u2010Kyeong","family":"Jo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,12,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365549409008634"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20989"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2009.197822"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000895"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2009.05.002"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22343"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2006.02.019"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018666"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2009.08.014"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/21.4.924"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.17.2.323-347.2004"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08938"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1191\/1352458502ms817oa"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1703"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.49.32608"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0704908104"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2008\/614345"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903811"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0806512"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.2.1199"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.1101"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.03.012"},{"key":"e_1_2_6_24_1","first-page":"413","article-title":"Tuberculous meningitis: Problems in pathogenesis and treatment","volume":"58","author":"Horne NW","year":"1951","journal-title":"Edinb Med J"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1631"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200940185"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041892"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903019"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00730.x"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-008-9222-3"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001954"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2011.72"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011145"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2008.03.003"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2011.01.005"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2010.01450.x"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2010.01.017"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1980"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000661"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737855"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.6.3353"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.2.838"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4402195"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-13-05334.2002"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1010337107"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.17.4.942-964.2004"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00042-07"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20906"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03872.x"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201141436"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1097\/00126334-200304010-00019"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2010.05.015"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-4-27"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fglia.22448","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.22448","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T00:01:19Z","timestamp":1700611279000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.22448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12,27]]},"references-count":52,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,3]]}},"alternative-id":["10.1002\/glia.22448"],"URL":"https:\/\/doi.org\/10.1002\/glia.22448","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12,27]]}}}