{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T13:28:25Z","timestamp":1776259705162,"version":"3.50.1"},"posted":{"date-parts":[[2026,4,11]]},"group-title":"Immunology","reference-count":28,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:00:00Z","timestamp":1775865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  <jats:italic>Francisella tularensis<\/jats:italic>\n                  is a Gram-negative bacterium that causes tularemia, a fatal zoonotic disease.\n                  <jats:italic>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                  <jats:italic>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 proinflammatory cytokines required for controlling\n                  <jats:italic>F. tularensis<\/jats:italic>\n                  infection. Prior studies have shown that\n                  <jats:italic>F. tularensis<\/jats:italic>\n                  actively suppresses Aim2 inflammasome activation; however, the underlying mechanism remains unknown. We hypothesized that\n                  <jats:italic>F. tularensis<\/jats:italic>\n                  suppresses Aim2-mediated responses by modulating the intracellular redox environment. We utilized an\n                  <jats:italic>F. tularensis<\/jats:italic>\n                  mutant lacking OxyR (\u0394\n                  <jats:italic>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                  <jats:italic>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                  <jats:italic>oxyR<\/jats:italic>\n                  -infected macrophages than in controls. These changes were absent in \u0394\n                  <jats:italic>oxyR<\/jats:italic>\n                  -infected NADPH oxidase-deficient macrophages, which are unable to generate reactive oxygen species. Collectively, these findings demonstrate that macrophage redox environment plays a key role in activating signaling components required for Aim2 inflammasome activation. This work advances our understanding of how\n                  <jats:italic>F. tularensis<\/jats:italic>\n                  -encoded factors subvert host innate immune defenses.\n                <\/jats:p>","DOI":"10.64898\/2026.04.09.717616","type":"posted-content","created":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T09:40:18Z","timestamp":1775900418000},"source":"Crossref","is-referenced-by-count":0,"title":["Antioxidant defenses of\n                  <i>Francisella tularensis<\/i>\n                  perturb Aim2 Inflammasome Activation"],"prefix":"10.64898","author":[{"given":"Zhuo","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Albany College of Pharmacy and Health Sciences, Albany, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Albany College of Pharmacy and Health Sciences, Albany, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayla","family":"Fantone","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Albany College of Pharmacy and Health Sciences, Albany, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5459-3225","authenticated-orcid":false,"given":"Chandra Shekhar","family":"Bakshi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meenakshi","family":"Malik","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Albany College of Pharmacy and Health Sciences, Albany, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041505350891000_2026.04.09.717616v1.1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1925.02660430001001"},{"key":"2026041505350891000_2026.04.09.717616v1.2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.21.2763"},{"key":"2026041505350891000_2026.04.09.717616v1.3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-ento-011019-025134"},{"key":"2026041505350891000_2026.04.09.717616v1.4","doi-asserted-by":"crossref","unstructured":"Kingry LC , Petersen JM . 2014. Comparative review of Francisella tularensis and Francisella novicida. Front Cell Infect Microbiol 4.","DOI":"10.3389\/fcimb.2014.00035"},{"key":"2026041505350891000_2026.04.09.717616v1.5","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00534-09"},{"key":"2026041505350891000_2026.04.09.717616v1.6","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00266-06"},{"key":"2026041505350891000_2026.04.09.717616v1.7","doi-asserted-by":"crossref","first-page":"e0213699","DOI":"10.1371\/journal.pone.0213699","article-title":"Role of peroxiredoxin of the AhpC\/TSA family in antioxidant defense mechanisms of Francisella tularensis","volume":"14","year":"2019","journal-title":"PLoS One"},{"key":"2026041505350891000_2026.04.09.717616v1.8","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13426"},{"key":"2026041505350891000_2026.04.09.717616v1.9","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01717-06"},{"key":"2026041505350891000_2026.04.09.717616v1.10","first-page":"14","article-title":"Lack of OxyR and KatG Results in Extreme Susceptibility of Francisella tularensis LVS to Oxidative Stress and Marked Attenuation In vivo","volume":"1","year":"2017","journal-title":"Frontiers in Cellular and Infection Microbiology"},{"key":"2026041505350891000_2026.04.09.717616v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.02.096"},{"key":"2026041505350891000_2026.04.09.717616v1.12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.01022.x"},{"key":"2026041505350891000_2026.04.09.717616v1.13","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062665"},{"key":"2026041505350891000_2026.04.09.717616v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3119"},{"key":"2026041505350891000_2026.04.09.717616v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.07.006"},{"key":"2026041505350891000_2026.04.09.717616v1.16","doi-asserted-by":"crossref","unstructured":"Crane DD , Bauler TJ , Wehrly TD , Bosio CM . 2014. 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