{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:52:43Z","timestamp":1792788763510,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012020","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T00:00:00Z","timestamp":1716508800000}}],"reference-count":77,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T00:00:00Z","timestamp":1715644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI153586"],"award-info":[{"award-number":["AI153586"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI132674"],"award-info":[{"award-number":["AI132674"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI156536"],"award-info":[{"award-number":["AI156536"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI179997"],"award-info":[{"award-number":["AI179997"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007865","name":"University of Texas Medical Branch","doi-asserted-by":"publisher","award":["IHII NTT Startup grant"],"award-info":[{"award-number":["IHII NTT Startup grant"]}],"id":[{"id":"10.13039\/100007865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007865","name":"University of Texas Medical Branch","doi-asserted-by":"publisher","award":["IHII Data Acquisition grant"],"award-info":[{"award-number":["IHII Data Acquisition grant"]}],"id":[{"id":"10.13039\/100007865","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Gulf Coast Center for Precision Environmental Health","award":["86445"],"award-info":[{"award-number":["86445"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Scrub typhus is an acute febrile disease due to\n                    <jats:italic>Orientia tsutsugamushi<\/jats:italic>\n                    (\n                    <jats:italic>Ot<\/jats:italic>\n                    ) infection and can be life-threatening with organ failure, hemorrhage, and fatality. Yet, little is known as to how the host reacts to\n                    <jats:italic>Ot<\/jats:italic>\n                    bacteria at early stages of infection; no reports have addressed the functional roles of type I versus type II interferon (IFN) responses in scrub typhus. In this study, we used comprehensive intradermal (i.d.) inoculation models and two clinically predominant\n                    <jats:italic>Ot<\/jats:italic>\n                    strains (Karp and Gilliam) to uncover early immune events. Karp infection induced sequential expression of\n                    <jats:italic>Ifnb<\/jats:italic>\n                    and\n                    <jats:italic>Ifng<\/jats:italic>\n                    in inflamed skin and draining lymph nodes at days 1 and 3 post-infection. Using double\n                    <jats:italic>Ifnar1<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    <jats:italic>Ifngr1<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    and\n                    <jats:italic>Stat1<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice, we found that deficiency in IFN\/STAT1 signaling resulted in lethal infection with profound pathology and skin eschar lesions, which resembled to human scrub typhus. Further analyses demonstrated that deficiency in IFN-\u03b3, but not IFN-I, resulted in impaired NK cell and macrophage activation and uncontrolled bacterial growth and dissemination, leading to metabolic dysregulation, excessive inflammatory cell infiltration, and exacerbated tissue damage. NK cells were found to be the major cellular source of innate IFN-\u03b3, contributing to the initial\n                    <jats:italic>Ot<\/jats:italic>\n                    control in the draining lymph nodes. In vitro studies with dendritic cell cultures revealed a superior antibacterial effect offered by IFN-\u03b3 than IFN-\u03b2. Comparative in vivo studies with Karp- and Gilliam-infection revealed a crucial role of IFN-\u03b3 signaling in protection against progression of eschar lesions and\n                    <jats:italic>Ot<\/jats:italic>\n                    infection lethality. Additionally, our i.d. mouse models of lethal infection with eschar lesions are promising tools for immunological study and vaccine development for scrub typhus.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1012020","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T13:48:50Z","timestamp":1715694530000},"page":"e1012020","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Lack of the IFN-\u03b3 signal leads to lethal Orientia tsutsugamushi infection in mice with skin eschar lesions"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9557-1847","authenticated-orcid":true,"given":"Yuejin","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keer","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaren","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"Soong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,14]]},"reference":[{"issue":"1","key":"ppat.1012020.ref001","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3390\/tropicalmed3010008","article-title":"A Review of Scrub Typhus 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Taylor","year":"2015","journal-title":"PLoS Negl Trop Dis."},{"issue":"1","key":"ppat.1012020.ref005","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3390\/tropicalmed3010011","article-title":"Scrub Typhus: No Longer Restricted to the Tsutsugamushi Triangle","volume":"3","author":"J Jiang","year":"2018","journal-title":"Trop Med Infect Dis"},{"issue":"10","key":"ppat.1012020.ref006","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1056\/NEJMoa1603657","article-title":"Endemic Scrub Typhus in South America","volume":"375","author":"T Weitzel","year":"2016","journal-title":"N Engl J Med"},{"issue":"8","key":"ppat.1012020.ref007","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.3201\/eid2908.230528","article-title":"Detection of Orientia spp. Bacteria in Field-Collected Free-Living Eutrombicula Chigger Mites, United States","volume":"29","author":"K Chen","year":"2023","journal-title":"Emerg Infect 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Trent","year":"2020","journal-title":"PLoS Negl Trop Dis"},{"issue":"7","key":"ppat.1012020.ref011","doi-asserted-by":"crossref","first-page":"e0005765","DOI":"10.1371\/journal.pntd.0005765","article-title":"Type 1-skewed neuroinflammation and vascular damage associated with Orientia tsutsugamushi infection in mice.","volume":"11","author":"L Soong","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"issue":"9","key":"ppat.1012020.ref012","doi-asserted-by":"crossref","first-page":"e3191","DOI":"10.1371\/journal.pntd.0003191","article-title":"Strong type 1, but impaired type 2, immune responses contribute to Orientia tsutsugamushi-induced pathology in mice.","volume":"8","author":"L Soong","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"issue":"7","key":"ppat.1012020.ref013","doi-asserted-by":"crossref","first-page":"e2966","DOI":"10.1371\/journal.pntd.0002966","article-title":"Hematogenously disseminated Orientia tsutsugamushi-infected murine model of scrub typhus 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Innate Immune Response and Lung Injury During Orientia tsutsugamushi Infection","volume":"10","author":"B Trent","year":"2019","journal-title":"Front Microbiol"},{"issue":"5","key":"ppat.1012020.ref037","doi-asserted-by":"crossref","first-page":"806","DOI":"10.4269\/ajtmh.2007.76.806","article-title":"Distribution of eschars on the body of scrub typhus patients: a prospective study","volume":"76","author":"DM Kim","year":"2007","journal-title":"Am J Trop Med Hyg"},{"issue":"1","key":"ppat.1012020.ref038","doi-asserted-by":"crossref","first-page":"e1466","DOI":"10.1371\/journal.pntd.0001466","article-title":"Orientia tsutsugamushi in human scrub typhus eschars shows tropism for dendritic cells and monocytes rather than endothelium","volume":"6","author":"DH Paris","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"issue":"6","key":"ppat.1012020.ref039","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.4269\/ajtmh.16-0583","article-title":"Evolution of Eschar in Scrub 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Knipfer","year":"2019","journal-title":"J Exp Med"},{"issue":"23","key":"ppat.1012020.ref043","doi-asserted-by":"crossref","first-page":"6086","DOI":"10.1073\/pnas.1621280114","article-title":"CCR8(+)FOXp3(+) T(reg) cells as master drivers of immune regulation.","volume":"114","author":"Y Barsheshet","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"ppat.1012020.ref044","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/cmi.2012.23","article-title":"The CXCL12\/CXCR4 axis is involved in the maintenance of Th2 bias at the maternal\/fetal interface in early human pregnancy","volume":"9","author":"HL Piao","year":"2012","journal-title":"Cell Mol Immunol"},{"issue":"3","key":"ppat.1012020.ref045","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1089\/vbz.2008.0149","article-title":"Does IL-17 play a role in hepatic dysfunction of scrub typhus patients?","volume":"10","author":"HJ Yoon","year":"2010","journal-title":"Vector Borne Zoonotic 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