{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:53:37Z","timestamp":1792788817996,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011791","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000}}],"reference-count":78,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T00:00:00Z","timestamp":1699833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"College of Medicine, UIC, Department of Pathology Start-up funds"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Ehrlichia<\/jats:italic>\n                    is Gram negative obligate intracellular bacterium that cause human monocytotropic ehrlichiosis (HME). HME is characterized by acute liver damage and inflammation that may progress to fatal toxic shock. We previously showed that fatal ehrlichiosis is due to deleterious activation of inflammasome pathways, which causes excessive inflammation and liver injury. Mammalian cells have developed mechanisms to control oxidative stress via regulation of nuclear factor erythroid 2 related 2 (NRF2) signaling. However, the contribution of NRF2 signaling to\n                    <jats:italic>Ehrlichia<\/jats:italic>\n                    -induced inflammasome activation and liver damage remains elusive. In this study, we investigated the contribution of NRF2 signaling in hepatocytes (HCs) to the pathogenesis of\n                    <jats:italic>Ehrlichia<\/jats:italic>\n                    -induced liver injury following infection with virulent\n                    <jats:italic>Ixodes ovatus Ehrlichia<\/jats:italic>\n                    (IOE, AKA\n                    <jats:italic>E<\/jats:italic>\n                    .\n                    <jats:italic>japonica<\/jats:italic>\n                    ). Employing murine model of fatal ehrlichiosis, we found that virulent IOE inhibited NRF2 signaling in liver tissue of infected mice and in HCs as evidenced by downregulation of NRF2 expression, and downstream target GPX4, as well as decreased NRF2 nuclear translocation, a key step in NRF2 activation. This was associated with activation of non-canonical inflammasomes pathway marked by activation of caspase 11, accumulation of reactive oxygen species (ROS), mitochondrial dysfunction, and endoplasmic reticulum (ER) stress. Mechanistically, treatment of IOE-infected HCs with the antioxidant 3H-1,2-Dithiole-3-Thione (D3T), that induces NRF2 activation, attenuated oxidative stress and caspase 11 activation, as well as restored cell viability. Importantly, treatment of IOE-infected mice with D3T resulted in attenuated liver pathology, decreased inflammation, enhanced bacterial clearance, prolonged survival, and resistance to fatal ehrlichiosis. Our study reveals, for the first time, that targeting anti-oxidative signaling pathway is a key approach in the treatment of severe and potential\n                    <jats:italic>Ehrlichia<\/jats:italic>\n                    -induced acute liver injury and sepsis.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011791","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T13:38:58Z","timestamp":1699882738000},"page":"e1011791","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Evasion of host antioxidative response via disruption of NRF2 signaling in fatal Ehrlichia-induced liver injury"],"prefix":"10.1371","volume":"19","author":[{"given":"Aditya Kumar","family":"Sharma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdeljabar","family":"El Andaloussi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2399-7582","authenticated-orcid":true,"given":"Nahed","family":"Ismail","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,11,13]]},"reference":[{"issue":"5","key":"ppat.1011791.ref001","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.cellsig.2012.01.008","article-title":"Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling","volume":"24","author":"PD Ray","year":"2012","journal-title":"Cell Signal"},{"issue":"2 Suppl 1","key":"ppat.1011791.ref002","doi-asserted-by":"crossref","first-page":"S63","DOI":"10.1002\/hep.20957","article-title":"Alcohol and oxidative liver injury","volume":"43","author":"A Dey","year":"2006","journal-title":"Hepatology"},{"key":"ppat.1011791.ref003","doi-asserted-by":"crossref","first-page":"9547613","DOI":"10.1155\/2018\/9547613","article-title":"Role of Oxidative Stress in Pathophysiology of Nonalcoholic Fatty Liver Disease.","volume":"2018","author":"M Masarone","year":"2018","journal-title":"Oxid Med Cell Longev"},{"key":"ppat.1011791.ref004","first-page":"669","volume-title":"Chapter 32\u2014Oxidative\/nitrosative stress and hepatic encephalopathy.","author":"D H\u00e4ussinger","year":"2020"},{"issue":"17","key":"ppat.1011791.ref005","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1089\/ars.2017.7342","article-title":"Transcriptional Regulation by Nrf2","volume":"29","author":"C Tonelli","year":"2018","journal-title":"Antioxid Redox Signal"},{"issue":"1","key":"ppat.1011791.ref006","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.cll.2009.10.004","article-title":"Human ehrlichiosis and anaplasmosis","volume":"30","author":"N Ismail","year":"2010","journal-title":"Clin Lab Med"},{"issue":"1","key":"ppat.1011791.ref007","article-title":"Review: Protective Immunity and Immunopathology of Ehrlichiosis","volume":"2","author":"N Ismail","year":"2022","journal-title":"Zoonoses (Burlingt)."},{"issue":"2","key":"ppat.1011791.ref008","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/S0002-9440(10)64018-7","article-title":"Animal model of fatal human monocytotropic ehrlichiosis","volume":"158","author":"EA Sotomayor","year":"2001","journal-title":"Am J Pathol"},{"issue":"6","key":"ppat.1011791.ref009","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.immuni.2019.10.004","article-title":"Liver Is a Generative Site for the B Cell Response to Ehrlichia muris","volume":"51","author":"N Trivedi","year":"2019","journal-title":"Immunity"},{"issue":"1","key":"ppat.1011791.ref010","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/hep4.1608","article-title":"Interferon Type I Regulates Inflammasome Activation and High Mobility Group Box 1 Translocation in Hepatocytes During Ehrlichia-Induced Acute Liver Injury.","volume":"5","author":"M Kader","year":"2021","journal-title":"Hepatol Commun"},{"issue":"12","key":"ppat.1011791.ref011","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.1128\/iai.56.12.3209-3215.1988","article-title":"Lack of lysosomal fusion with phagosomes containing Ehrlichia risticii in P388D1 cells: abrogation of inhibition with oxytetracycline","volume":"56","author":"MY Wells","year":"1988","journal-title":"Infect Immun"},{"key":"ppat.1011791.ref012","doi-asserted-by":"crossref","first-page":"642771","DOI":"10.3389\/fimmu.2021.642771","article-title":"Anaplasmataceae: Dichotomous Autophagic Interplay for Infection.","volume":"12","author":"LL Patterson","year":"2021","journal-title":"Front Immunol."},{"issue":"10","key":"ppat.1011791.ref013","doi-asserted-by":"crossref","first-page":"e1006644","DOI":"10.1371\/journal.ppat.1006644","article-title":"MyD88-dependent inflammasome activation and autophagy inhibition contributes to Ehrlichia-induced liver injury and toxic shock","volume":"13","author":"M Kader","year":"2017","journal-title":"PLoS Pathog"},{"issue":"3","key":"ppat.1011791.ref014","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.micinf.2010.10.021","article-title":"Obligate intracellular bacterium Ehrlichia inhibiting mitochondrial activity","volume":"13","author":"Y Liu","year":"2011","journal-title":"Microbes Infect"},{"issue":"1","key":"ppat.1011791.ref015","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1097\/SLA.0000000000000287","article-title":"Nrf2 activation protects the liver from ischemia\/reperfusion injury in mice","volume":"260","author":"K Kudoh","year":"2014","journal-title":"Ann Surg"},{"key":"ppat.1011791.ref016","first-page":"4505513","article-title":"Nrf2-Mediated Ferroptosis Inhibition Exerts a Protective Effect on Acute-on-Chronic Liver Failure.","volume":"2022","author":"J Wu","year":"2022","journal-title":"Oxid Med Cell Longev"},{"issue":"1","key":"ppat.1011791.ref017","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1093\/toxsci\/kfn079","article-title":"Genetic or pharmacologic amplification of nrf2 signaling inhibits acute inflammatory liver injury in mice","volume":"104","author":"WO Osburn","year":"2008","journal-title":"Toxicol Sci"},{"issue":"13","key":"ppat.1011791.ref018","article-title":"NRF2, a Transcription Factor for Stress Response and Beyond.","volume":"21","author":"F He","year":"2020","journal-title":"Int J Mol Sci."},{"key":"ppat.1011791.ref019","doi-asserted-by":"crossref","first-page":"101107","DOI":"10.1016\/j.redox.2019.101107","article-title":"NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis.","volume":"23","author":"M Dodson","year":"2019","journal-title":"Redox Biol."},{"key":"ppat.1011791.ref020","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/B978-0-12-804274-8.00028-X","article-title":"Nrf2: a key regulator of redox signaling in liver diseases","author":"K Kim","year":"2017","journal-title":"Liver Pathophysiology: Elsevier"},{"issue":"11","key":"ppat.1011791.ref021","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20220504","article-title":"GPX4 regulates cellular necrosis and host resistance in Mycobacterium tuberculosis infection","volume":"219","author":"EP Amaral","year":"2022","journal-title":"J Exp Med"},{"issue":"18","key":"ppat.1011791.ref022","doi-asserted-by":"crossref","first-page":"1800311","DOI":"10.1002\/pmic.201800311","article-title":"GPX4 at the crossroads of lipid homeostasis and ferroptosis","volume":"19","author":"GC Forcina","year":"2019","journal-title":"Proteomics"},{"key":"ppat.1011791.ref023","doi-asserted-by":"crossref","first-page":"114365","DOI":"10.1016\/j.bcp.2020.114365","article-title":"Insights into the role of GPX3, a highly efficient plasma antioxidant, in cancer","volume":"184","author":"S Nirgude","year":"2021","journal-title":"Biochemical pharmacology"},{"issue":"8","key":"ppat.1011791.ref024","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12082197","article-title":"Extracellular Glutathione Peroxidase GPx3 and Its Role in Cancer.","volume":"12","author":"C Chang","year":"2020","journal-title":"Cancers (Basel)."},{"key":"ppat.1011791.ref025","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.freeradbiomed.2013.05.028","article-title":"A Txnrd1-dependent metabolic switch alters hepatic lipogenesis, glycogen storage, and detoxification","volume":"63","author":"SV Iverson","year":"2013","journal-title":"Free Radic Biol Med"},{"key":"ppat.1011791.ref026","doi-asserted-by":"crossref","first-page":"101950","DOI":"10.1016\/j.redox.2021.101950","article-title":"The diverse functionality of NQO1 and its roles in redox control.","volume":"41","author":"D Ross","year":"2021","journal-title":"Redox Biol."},{"key":"ppat.1011791.ref027","doi-asserted-by":"crossref","first-page":"595","DOI":"10.3389\/fphys.2017.00595","article-title":"Functions of NQO1 in cellular protection and CoQ10 metabolism and its potential role as a redox sensitive molecular switch","volume":"8","author":"D Ross","year":"2017","journal-title":"Frontiers in physiology"},{"issue":"11","key":"ppat.1011791.ref028","doi-asserted-by":"crossref","first-page":"609","DOI":"10.5483\/BMBRep.2015.48.11.190","article-title":"Implications of NQO1 in cancer therapy","volume":"48","author":"ET Oh","year":"2015","journal-title":"BMB Rep"},{"issue":"1","key":"ppat.1011791.ref029","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1089\/ars.2012.4754","article-title":"The predicted molecular weight of Nrf2: it is what it is not","volume":"18","author":"A Lau","year":"2013","journal-title":"Antioxid Redox Signal"},{"issue":"36","key":"ppat.1011791.ref030","doi-asserted-by":"crossref","first-page":"34286","DOI":"10.1074\/jbc.M305327200","article-title":"Distinct promoters determine alternative transcription of gpx-4 into phospholipid-hydroperoxide glutathione peroxidase variants","volume":"278","author":"M Maiorino","year":"2003","journal-title":"J Biol Chem"},{"issue":"1","key":"ppat.1011791.ref031","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s40164-023-00427-w","article-title":"Ferroptosis: a novel regulated cell death participating in cellular stress response, radiotherapy, and immunotherapy","volume":"12","author":"X Zheng","year":"2023","journal-title":"Exp Hematol Oncol"},{"issue":"11","key":"ppat.1011791.ref032","doi-asserted-by":"crossref","first-page":"109235","DOI":"10.1016\/j.celrep.2021.109235","article-title":"The glutathione peroxidase Gpx4 prevents lipid peroxidation and ferroptosis to sustain Treg cell activation and suppression of antitumor immunity","volume":"35","author":"C Xu","year":"2021","journal-title":"Cell Rep"},{"issue":"2","key":"ppat.1011791.ref033","doi-asserted-by":"crossref","first-page":"e16845","DOI":"10.1371\/journal.pone.0016845","article-title":"Stabilization of Nrf2 protein by D3T provides protection against ethanol-induced apoptosis in PC12 cells.","volume":"6","author":"J Dong","year":"2011","journal-title":"PLoS One."},{"key":"ppat.1011791.ref034","doi-asserted-by":"crossref","first-page":"25525","DOI":"10.1038\/srep25525","article-title":"3H-1,2-dithiole-3-thione protects retinal pigment epithelium cells against Ultra-violet radiation via activation of Akt-mTORC1-dependent Nrf2-HO-1 signaling.","volume":"6","author":"KR Li","year":"2016","journal-title":"Sci Rep."},{"issue":"1","key":"ppat.1011791.ref035","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13024-020-00367-7","article-title":"PINK1 and Parkin mitochondrial quality control: a source of regional vulnerability in Parkinson\u2019s disease.","volume":"15","author":"P Ge","year":"2020","journal-title":"Mol Neurodegener."},{"key":"ppat.1011791.ref036","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.phrs.2015.09.020","article-title":"Targeting Pink1-Parkin-mediated mitophagy for treating liver injury","volume":"102","author":"JA Williams","year":"2015","journal-title":"Pharmacological research"},{"issue":"5","key":"ppat.1011791.ref037","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1073\/pnas.0709336105","article-title":"The PINK1\/Parkin pathway regulates mitochondrial morphology","volume":"105","author":"AC Poole","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"ppat.1011791.ref038","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/emmm.200900024","article-title":"PINK1 function in health and disease","volume":"1","author":"E Deas","year":"2009","journal-title":"EMBO Mol Med"},{"issue":"11","key":"ppat.1011791.ref039","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1111\/febs.13249","article-title":"Parkin structure and function.","volume":"282","author":"M Seirafi","year":"2015","journal-title":"FEBS J."},{"issue":"4","key":"ppat.1011791.ref040","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1093\/emboj\/21.4.835","article-title":"ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family","volume":"21","author":"T Anelli","year":"2002","journal-title":"EMBO J"},{"key":"ppat.1011791.ref041","first-page":"133","article-title":"The pivotal role of ERp44 in patrolling protein secretion","author":"T Tempio","year":"2020","journal-title":"J Cell Sci"},{"issue":"2","key":"ppat.1011791.ref042","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nrm3270","article-title":"The unfolded protein response: controlling cell fate decisions under ER stress and beyond","volume":"13","author":"C. Hetz","year":"2012","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ppat.1011791.ref043","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3389\/fonc.2017.00078","article-title":"Endoplasmic Reticulum Stress, Unfolded Protein Response, and Cancer Cell Fate","volume":"7","author":"M Corazzari","year":"2017","journal-title":"Front Oncol"},{"issue":"3","key":"ppat.1011791.ref044","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1093\/jb\/mvr143","article-title":"CHOP is a multifunctional transcription factor in the ER stress response","volume":"151","author":"H. Nishitoh","year":"2012","journal-title":"J Biochem"},{"issue":"4","key":"ppat.1011791.ref045","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/sj.cdd.4401373","article-title":"Roles of CHOP\/GADD153 in endoplasmic reticulum stress","volume":"11","author":"S Oyadomari","year":"2004","journal-title":"Cell Death Differ"},{"issue":"10","key":"ppat.1011791.ref046","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21103468","article-title":"EDEM1 Drives Misfolded Protein Degradation via ERAD and Exploits ER-Phagy as Back-Up Mechanism When ERAD Is Impaired.","volume":"21","author":"M Chiritoiu","year":"2020","journal-title":"Int J Mol Sci."},{"issue":"11","key":"ppat.1011791.ref047","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1096\/fj.02-1184fje","article-title":"The function of GADD34 is a recovery from a shutoff of protein synthesis induced by ER stress: elucidation by GADD34-deficient mice","volume":"17","author":"E Kojima","year":"2003","journal-title":"Faseb j"},{"issue":"5","key":"ppat.1011791.ref048","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1038\/cdd.2017.53","article-title":"DR5 and caspase-8 are dispensable in ER stress-induced apoptosis","volume":"24","author":"JA Glab","year":"2017","journal-title":"Cell Death Differ"},{"key":"ppat.1011791.ref049","doi-asserted-by":"crossref","first-page":"39838","DOI":"10.1038\/srep39838","article-title":"Tauroursodeoxycholic acid reduces ER stress by regulating of Akt-dependent cellular prion protein","volume":"6","author":"YM Yoon","year":"2016","journal-title":"Sci Rep"},{"issue":"5","key":"ppat.1011791.ref050","doi-asserted-by":"crossref","first-page":"e0196785","DOI":"10.1371\/journal.pone.0196785","article-title":"Tauroursodeoxycholic acid (TUDCA) alleviates endoplasmic reticulum stress of nuclear donor cells under serum starvation.","volume":"13","author":"Y Zhang","year":"2018","journal-title":"PLoS One."},{"key":"ppat.1011791.ref051","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/B978-0-12-386454-3.00345-6","article-title":"Oxidative stress.","author":"K Shankar","year":"2014","journal-title":"Encyclopedia of toxicology"},{"key":"ppat.1011791.ref052","first-page":"2017","article-title":"Oxidative stress: harms and benefits for human health.","author":"G Pizzino","year":"2017","journal-title":"Oxidative medicine and cellular longevity."},{"key":"ppat.1011791.ref053","doi-asserted-by":"crossref","first-page":"597134","DOI":"10.1155\/2015\/597134","article-title":"The Dual Role of Nrf2 in Nonalcoholic Fatty Liver Disease: Regulation of Antioxidant Defenses and Hepatic Lipid Metabolism","volume":"2015","author":"SS Chambel","year":"2015","journal-title":"Biomed Res Int"},{"issue":"1","key":"ppat.1011791.ref054","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/2045-3701-2-40","article-title":"Anti-oxidative stress regulator NF-E2-related factor 2 mediates the adaptive induction of antioxidant and detoxifying enzymes by lipid peroxidation metabolite 4-hydroxynonenal.","volume":"2","author":"Y Huang","year":"2012","journal-title":"Cell & Bioscience."},{"issue":"11","key":"ppat.1011791.ref055","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/s41419-022-05363-x","article-title":"USF2-mediated upregulation of TXNRD1 contributes to hepatocellular carcinoma progression by activating Akt\/mTOR signaling","volume":"13","author":"WY Huang","year":"2022","journal-title":"Cell Death Dis"},{"key":"ppat.1011791.ref056","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/B978-0-12-804274-8.00028-X","volume-title":"Liver Pathophysiology","author":"KM Kim","year":"2017"},{"issue":"1","key":"ppat.1011791.ref057","doi-asserted-by":"crossref","first-page":"12890","DOI":"10.1038\/s41598-021-92369-8","article-title":"Overexpression of ferroptosis defense enzyme Gpx4 retards motor neuron disease of SOD1G93A mice.","volume":"11","author":"L Chen","year":"2021","journal-title":"Sci Rep."},{"key":"ppat.1011791.ref058","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s40364-020-00229-w","article-title":"Novel insights on targeting ferroptosis in cancer therapy","volume":"8","author":"S Zuo","year":"2020","journal-title":"Biomark Res"},{"key":"ppat.1011791.ref059","doi-asserted-by":"crossref","DOI":"10.1128\/MCB.00099-20","article-title":"The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway","volume":"40","author":"L Baird","year":"2020","journal-title":"Mol Cell Biol"},{"key":"ppat.1011791.ref060","doi-asserted-by":"crossref","first-page":"e0000223","DOI":"10.1128\/iai.00002-23","article-title":"Ehrlichia Notch signaling induction promotes XIAP stability and inhibits apoptosis","volume":"2023","author":"LL Patterson","year":"2023","journal-title":"Infect Immun"},{"issue":"2","key":"ppat.1011791.ref061","doi-asserted-by":"crossref","first-page":"pgad017","DOI":"10.1093\/pnasnexus\/pgad017","article-title":"Inhibition of Ehrlichia chaffeensis infection by cell-permeable macrocyclic peptides that bind type IV secretion effector Etf-1.","volume":"2","author":"M Lin","year":"2023","journal-title":"PNAS nexus."},{"issue":"1","key":"ppat.1011791.ref062","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1128\/IAI.72.1.498-507.2004","article-title":"Survival strategy of obligately intracellular Ehrlichia chaffeensis: novel modulation of immune response and host cell cycles","volume":"72","author":"JZ Zhang","year":"2004","journal-title":"Infect Immun"},{"issue":"2","key":"ppat.1011791.ref063","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.cll.2017.01.006","article-title":"Tick-Borne Emerging Infections: Ehrlichiosis and Anaplasmosis.","volume":"37","author":"N Ismail","year":"2017","journal-title":"Clin Lab Med"},{"issue":"7","key":"ppat.1011791.ref064","doi-asserted-by":"crossref","first-page":"3604","DOI":"10.1128\/IAI.02028-06","article-title":"Virulence potential of Ehrlichia chaffeensis strains of distinct genome sequences","volume":"75","author":"K Miura","year":"2007","journal-title":"Infect Immun"},{"issue":"7","key":"ppat.1011791.ref065","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1099\/ijsem.0.001896","article-title":"Proposal to reclassify Ehrlichia muris as Ehrlichia muris subsp. muris subsp. nov. and description of Ehrlichia muris subsp. eauclairensis subsp. nov., a newly recognized tick-borne pathogen of humans","volume":"67","author":"BS Pritt","year":"2017","journal-title":"Int J Syst Evol Microbiol"},{"issue":"6","key":"ppat.1011791.ref066","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1128\/IAI.02488-14","article-title":"Roles of reactive oxygen species-degrading enzymes of Francisella tularensis SCHU S4","volume":"83","author":"J Binesse","year":"2015","journal-title":"Infect Immun"},{"issue":"36","key":"ppat.1011791.ref067","doi-asserted-by":"crossref","first-page":"27553","DOI":"10.1074\/jbc.M110.144394","article-title":"Francisella tularensis antioxidants harness reactive oxygen species to restrict macrophage signaling and cytokine production","volume":"285","author":"AA Melillo","year":"2010","journal-title":"J Biol Chem"},{"issue":"11","key":"ppat.1011791.ref068","doi-asserted-by":"crossref","first-page":"7629","DOI":"10.1128\/IAI.73.11.7629-7636.2005","article-title":"Effects of Anaplasma phagocytophilum on host cell ferritin mRNA and protein levels","volume":"73","author":"JA Carlyon","year":"2005","journal-title":"Infect Immun"},{"issue":"1","key":"ppat.1011791.ref069","doi-asserted-by":"crossref","first-page":"13236","DOI":"10.1038\/s41598-019-49766-x","article-title":"The redox metabolic pathways function to limit Anaplasma phagocytophilum infection and multiplication while preserving fitness in tick vector cells.","volume":"9","author":"P Alberdi","year":"2019","journal-title":"Scientific Reports"},{"issue":"9","key":"ppat.1011791.ref070","doi-asserted-by":"crossref","first-page":"4642","DOI":"10.3390\/ijms22094642","article-title":"The Chemistry of Reactive Oxygen Species (ROS) Revisited: Outlining Their Role in Biological Macromolecules (DNA, Lipids and Proteins) and Induced Pathologies.","volume":"22","author":"CA Juan","year":"2021","journal-title":"International Journal of Molecular Sciences"},{"issue":"2","key":"ppat.1011791.ref071","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.molcel.2012.09.025","article-title":"Physiological roles of mitochondrial reactive oxygen species","volume":"48","author":"LA Sena","year":"2012","journal-title":"Mol Cell"},{"issue":"1","key":"ppat.1011791.ref072","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1186\/s13059-021-02496-8","article-title":"Gut bacterial metabolites modulate endoplasmic reticulum stress","volume":"22","author":"X Ke","year":"2021","journal-title":"Genome Biol"},{"key":"ppat.1011791.ref073","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.3389\/fimmu.2019.03147","article-title":"Insights Into the Role of Endoplasmic Reticulum Stress in Infectious Diseases.","volume":"10","author":"JA Choi","year":"2019","journal-title":"Front Immunol."},{"issue":"4","key":"ppat.1011791.ref074","article-title":"Ehrlichia chaffeensis TRP120 Activates Canonical Notch Signaling To Downregulate TLR2\/4 Expression and Promote Intracellular Survival.","volume":"7","author":"TT Lina","year":"2016","journal-title":"mBio."},{"issue":"5","key":"ppat.1011791.ref075","doi-asserted-by":"crossref","DOI":"10.1093\/femspd\/ftab026","article-title":"Ehrlichia TRP effectors: moonlighting, mimicry and infection.","volume":"79","author":"CD Byerly","year":"2021","journal-title":"Pathog Dis."},{"key":"ppat.1011791.ref076","doi-asserted-by":"crossref","first-page":"534","DOI":"10.3389\/fcimb.2017.00534","article-title":"Ehrlichia chaffeensis TRP32 Nucleomodulin Function and Localization Is Regulated by NEDD4L-Mediated Ubiquitination","volume":"7","author":"TR Farris","year":"2017","journal-title":"Front Cell Infect Microbiol"},{"issue":"5","key":"ppat.1011791.ref077","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1128\/IAI.00027-09","article-title":"An Ehrlichia chaffeensis tandem repeat protein interacts with multiple host targets involved in cell signaling, transcriptional regulation, and vesicle trafficking","volume":"77","author":"A Wakeel","year":"2009","journal-title":"Infect Immun"},{"issue":"10","key":"ppat.1011791.ref078","doi-asserted-by":"crossref","first-page":"4243","DOI":"10.1128\/IAI.00376-09","article-title":"Nuclear translocated Ehrlichia chaffeensis ankyrin protein interacts with a specific adenine-rich motif of host promoter and intronic Alu elements","volume":"77","author":"B Zhu","year":"2009","journal-title":"Infect Immun"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1011791","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011791","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T14:31:19Z","timestamp":1701095479000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011791"}},"subtitle":[],"editor":[{"given":"Richard D.","family":"Hayward","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,11,13]]},"references-count":78,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1011791","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,13]]}}}