{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:47:46Z","timestamp":1791899266610,"version":"4.3.4"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15AI107698"],"award-info":[{"award-number":["R15AI107698"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2026,10,13]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n Francisella tularensis<\/jats:italic>\n is a gram-negative bacterium that causes tularemia, a fatal zoonotic disease.\n F. tularensis<\/jats:italic>\n has been used in the bioweapon programs of several countries. Its potential use as a bioterrorism agent led the CDC to classify\n F. tularensis<\/jats:italic>\n as a Tier 1 Select Agent. The cytosolic sensor absent in melanoma 2 (Aim2) detects double-stranded DNA in the cytosol of infected cells and subsequently assembles a multiprotein complex known as the inflammasome. Inflammasome activation drives the secretion of IL-1\u03b2 and IL-18, key pro-inflammatory cytokines required for controlling\n F. tularensis<\/jats:italic>\n infection. Prior studies have shown that\n F. tularensis<\/jats:italic>\n actively suppresses Aim2 inflammasome activation; however, the underlying mechanism remains unknown. We hypothesized that\n F. tularensis<\/jats:italic>\n suppresses Aim2-mediated responses by modulating the intracellular redox environment. We utilized an\n F. tularensis<\/jats:italic>\n live vaccine strain (LVS) mutant lacking OxyR (\u0394\n oxyR<\/jats:italic>\n ), a transcriptional regulator that controls the expression of major antioxidant enzymes. Our results show that macrophages infected with the \u0394\n oxyR<\/jats:italic>\n mutant exhibit significantly higher levels of Aim2-dependent caspase-1 and IL-1\u03b2 than those infected with wild-type bacteria. The expression of interferon regulatory factor 1 and the guanylate-binding proteins GBP2 and GBP5, upstream signaling components of the Aim2 inflammasome, is markedly higher in \u0394\n oxyR<\/jats:italic>\n -infected macrophages than in controls. These changes were absent in \u0394\n oxyR<\/jats:italic>\n -infected NADPH oxidase-deficient macrophages, which are unable to generate reactive oxygen species. Collectively, these findings demonstrate that the macrophage redox environment plays a key role in activating the Aim2 inflammasome. This work advances understanding of how\n F. tularensis<\/jats:italic>\n -encoded factors subvert host innate immune defenses.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1128\/iai.00453-26","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:42:38Z","timestamp":1789479758000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Antioxidant defenses of\n Francisella tularensis<\/i>\n perturb Aim2 inflammasome activation"],"prefix":"10.1128","volume":"94","author":[{"given":"Zhuo","family":"Ma","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/014hfaw95","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Life Sciences, Albany College of Pharmacy and Health Sciences","place":["Albany, 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