{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:30:54Z","timestamp":1792737054639,"version":"4.5.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,9,4]],"date-time":"2018-09-04T00:00:00Z","timestamp":1536019200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2013R1A2A2A01007299"],"award-info":[{"award-number":["2013R1A2A2A01007299"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2018.02022","type":"journal-article","created":{"date-parts":[[2018,9,4]],"date-time":"2018-09-04T05:07:11Z","timestamp":1536037631000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":34,"title":["A Type I Interferon and IL-10 Induced by Orientia tsutsugamushi Infection Suppresses Antigen-Specific T Cells and Their Memory Responses"],"prefix":"10.3389","volume":"9","author":[{"given":"Chan-Ki","family":"Min","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-II","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na-Young","family":"Ha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Kyung","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thi Hai","family":"Yen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Je-In","family":"Youn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Kyung","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Soo","family":"Inn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung-Sik","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nam-Hyuk","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,9,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1038\/nri3806","article-title":"Regulation of antiviral T cell responses by type I interferons","volume":"15","author":"Crouse","year":"2015","journal-title":"Nat Rev Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/nri3787","article-title":"Type I interferons in infectious disease","volume":"15","author":"McNab","year":"2015","journal-title":"Nat Rev Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"9361802","DOI":"10.1155\/2017\/9361802","article-title":"Getting \u201cinside\u201d type I IFNs: type I IFNs in intracellular bacterial infections","volume":"2017","author":"Snyder","year":"2017","journal-title":"J Immunol Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"306","DOI":"10.3389\/fimmu.2014.00306","article-title":"Type I interferon in human autoimmunity","volume":"5","author":"Niewold","year":"2014","journal-title":"Front Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"214","DOI":"10.4110\/in.2017.17.4.214","article-title":"Cytokine signaling in tumor progression","volume":"17","author":"Lee","year":"2017","journal-title":"Immune Netw."},{"key":"B6","doi-asserted-by":"publisher","first-page":"609","DOI":"10.3389\/fimmu.2016.00609","article-title":"Type-I interferon responses: from friend to foe in the battle against chronic viral infection","volume":"7","author":"Murira","year":"2016","journal-title":"Front Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.it.2016.12.004","article-title":"Crosstalk between cytoplasmic RIG-I and STING sensing pathways","volume":"38","author":"Zevini","year":"2017","journal-title":"Trends Immunol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"652","DOI":"10.3389\/fimmu.2016.00652","article-title":"Type I interferons in bacterial infections: a balancing act","volume":"7","author":"Kovarik","year":"2016","journal-title":"Front Immunol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"7981","DOI":"10.1073\/pnas.0611553104","article-title":"The Orientia tsutsugamushi genome reveals massive proliferation of conjugative type IV secretion system and host-cell interaction genes","volume":"104","author":"Cho","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e00076-17","DOI":"10.1128\/CMR.00076-17","article-title":"An update on host-pathogen interplay and modulation of immune responses during Orientia tsutsugamushi infection","volume":"31","author":"Diaz","year":"2018","journal-title":"Clin Microbiol Rev."},{"key":"B11","doi-asserted-by":"publisher","first-page":"883","DOI":"10.3201\/eid2205.150953","article-title":"Q fever, scrub typhus, and rickettsial diseases in children, Kenya, 2011-2012","volume":"22","author":"Maina","year":"2016","journal-title":"Emerg Infect Dis."},{"key":"B12","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1056\/NEJMoa1603657","article-title":"endemic scrub typhus in South America","volume":"375","author":"Weitzel","year":"2016","journal-title":"N Engl J Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e0003971","DOI":"10.1371\/journal.pntd.0003971","article-title":"A systematic review of mortality from untreated scrub typhus (Orientia tsutsugamushi)","volume":"9","author":"Taylor","year":"2015","journal-title":"PLoS Negl Trop Dis."},{"key":"B14","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/j.1749-6632.2003.tb07391.x","article-title":"Outbreak of scrub typhus in southern India during the cooler months","volume":"990","author":"Mathai","year":"2003","journal-title":"Ann N Y Acad Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1177\/0049475517740310","article-title":"Scrub typhus reinfection","volume":"48","author":"Koralur","year":"2017","journal-title":"Trop Doct."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e0003814","DOI":"10.1371\/journal.pntd.0003814","article-title":"Urbanization of scrub typhus disease in South Korea","volume":"9","author":"Park","year":"2015","journal-title":"PLoS Negl Trop Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e0003585","DOI":"10.1371\/journal.pntd.0003585","article-title":"Immunization with an autotransporter protein of Orientia tsutsugamushi provides protective immunity against scrub typhus","volume":"9","author":"Ha","year":"2015","journal-title":"PLoS Negl Trop Dis."},{"key":"B18","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s12951-016-0229-2","article-title":"Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigen","volume":"14","author":"Ha","year":"2016","journal-title":"J Nanobiotechnol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1038\/modpathol.3880385","article-title":"Identification of the target cells of Orientia tsutsugamushi in human cases of scrub typhus","volume":"14","author":"Moron","year":"2001","journal-title":"Mod Pathol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e1789","DOI":"10.1371\/journal.pntd.0001789","article-title":"Phenotypic characterization of peripheral T cells and their dynamics in scrub typhus patients","volume":"6","author":"Cho","year":"2012","journal-title":"PLoS Negl Trop Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e116","DOI":"10.1038\/emi.2017.106","article-title":"Longevity of antibody and T-cell responses against outer membrane antigens of Orientia tsutsugamushi in scrub typhus patients","volume":"6","author":"Ha","year":"2017","journal-title":"Emerg Microbes Infect."},{"key":"B22","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1111\/j.1348-0421.2008.00098.x","article-title":"Activation of mitogen-activated protein kinases is involved in the induction of interferon beta gene in macrophages infected with Orientia tsutsugamushi","volume":"53","author":"Koo","year":"2009","journal-title":"Microbiol Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e99420","DOI":"10.1371\/journal.pone.0099420","article-title":"Intracellular bacteria interfere with dendritic cell functions: role of the type I interferon pathway","volume":"9","author":"Gorvel","year":"2014","journal-title":"PLoS ONE"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e1028","DOI":"10.1371\/journal.pntd.0001028","article-title":"Orientia tsutsugamushi stimulates an original gene expression program in monocytes: relationship with gene expression in patients with scrub typhus","volume":"5","author":"Tantibhedhyangkul","year":"2011","journal-title":"PLoS Negl Trop Dis."},{"key":"B25","doi-asserted-by":"crossref","first-page":"4134","DOI":"10.1128\/IAI.59.11.4134-4141.1991","article-title":"Comparative susceptibility to mouse interferons of Rickettsia tsutsugamushi strains with different virulence in mice and of Rickettsia rickettsii","volume":"59","author":"Hanson","year":"1991","journal-title":"Infect Immun."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1918","DOI":"10.1126\/science.8009221","article-title":"Functional role of type I and type II interferons in antiviral defense","volume":"264","author":"Muller","year":"1994","journal-title":"Science"},{"key":"B27","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S1074-7613(00)80596-8","article-title":"Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function","volume":"9","author":"Adachi","year":"1998","journal-title":"Immunity"},{"key":"B28","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1126\/science.1087262","article-title":"Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway","volume":"301","author":"Yamamoto","year":"2003","journal-title":"Science"},{"key":"B29","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/j.immuni.2006.04.004","article-title":"The specific and essential role of MAVS in antiviral innate immune responses","volume":"24","author":"Sun","year":"2006","journal-title":"Immunity"},{"key":"B30","doi-asserted-by":"publisher","first-page":"pdb.prot5080","DOI":"10.1101\/pdb.prot5080","article-title":"Bone Marrow-Derived Macrophages (BMM): isolation and applications","volume":"2008","author":"Weischenfeldt","year":"2008","journal-title":"CSH Protoc."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e1981","DOI":"10.1371\/journal.pntd.0001981","article-title":"Orientia tsutsugamushi subverts dendritic cell functions by escaping from autophagy and impairing their migration","volume":"7","author":"Choi","year":"2013","journal-title":"PLoS Negl Trop Dis."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e2966","DOI":"10.1371\/journal.pntd.0002966","article-title":"A hematogenously disseminated Orientia tsutsugamsushi-infected murine model of scrub typhus","volume":"8","author":"Shelite","year":"2014","journal-title":"PLoS Negl Trop Dis."},{"key":"B33","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(T)(-Delta Delta C) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B34","doi-asserted-by":"publisher","first-page":"155","DOI":"10.4167\/jbv.2013.43.2.155","article-title":"Molecular characterization of sca genes found in Orientia tsutsugamushi genome","volume":"43","author":"Ha","year":"2013","journal-title":"J Bacteriol Virol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1006\/jmbi.1994.1651","article-title":"Domains of interaction between alpha-interferon and its receptor components","volume":"243","author":"Uze","year":"1994","journal-title":"J Mol Biol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"3379","DOI":"10.1128\/IAI.00185-16","article-title":"Toll-like receptor 2 recognizes Orientia tsutsugamushi and increases susceptibility to murine experimental scrub typhus","volume":"84","author":"Gharaibeh","year":"2016","journal-title":"Infect Immun."},{"key":"B37","doi-asserted-by":"publisher","first-page":"4246","DOI":"10.1128\/IAI.01620-05","article-title":"Exploitation of the endocytic pathway by Orientia tsutsugamushi in nonprofessional phagocytes","volume":"74","author":"Chu","year":"2006","journal-title":"Infect Immun."},{"key":"B38","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1128\/IAI.00861-12","article-title":"Active escape of Orientia tsutsugamushi from cellular autophagy","volume":"81","author":"Ko","year":"2013","journal-title":"Infect Immun."},{"key":"B39","doi-asserted-by":"publisher","first-page":"4153","DOI":"10.1038\/emboj.2012.274","article-title":"RIG-I detects infection with live Listeria by sensing secreted bacterial nucleic acids","volume":"31","author":"Abdullah","year":"2012","journal-title":"EMBO J."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.15252\/embj.201488029","article-title":"Listeria monocytogenes induces IFN beta expression through an IFI16-, cGAS- and STING-dependent pathway","volume":"33","author":"Hansen","year":"2014","journal-title":"EMBO J."},{"key":"B41","doi-asserted-by":"crossref","first-page":"3629","DOI":"10.1128\/IAI.57.11.3629-3636.1989","article-title":"Listeriolysin-O is essential for virulence of Listeria monocytogenes - direct evidence obtained by gene complementation","volume":"57","author":"Cossart","year":"1989","journal-title":"Infect. Immun."},{"key":"B42","doi-asserted-by":"publisher","first-page":"3552","DOI":"10.4161\/cc.9.17.12792","article-title":"Molecular basis for an attenuated cytoplasmic dsRNA response in human embryonic stem cells","volume":"9","author":"Chen","year":"2010","journal-title":"Cell Cycle"},{"key":"B43","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1038\/srep00347","article-title":"STING mediates neuronal innate immune response following Japanese encephalitis virus infection","volume":"2","author":"Nazmi","year":"2012","journal-title":"Sci Rep."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e83639","DOI":"10.1371\/journal.pone.0083639","article-title":"Cell type-specific subcellular localization of phospho-TBK1 in response to cytoplasmic viral DNA","volume":"8","author":"Suzuki","year":"2013","journal-title":"PLoS ONE"},{"key":"B45","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1111\/j.1749-6632.1990.tb42219.x","article-title":"Interferon-alpha-beta and Rickettsia prowazekii - induction and sensitivity","volume":"590","author":"Turco","year":"1990","journal-title":"Ann NY Acad Sci."},{"key":"B46","doi-asserted-by":"publisher","first-page":"3733","DOI":"10.1128\/IAI.05008-11","article-title":"Beta interferon-mediated activation of signal transducer and activator of transcription protein 1 interferes with Rickettsia conorii replication in human endothelial cells","volume":"79","author":"Colonne","year":"2011","journal-title":"Infect Immun."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e0005408","DOI":"10.1371\/journal.pntd.0005408","article-title":"Diversification of Orientia tsutsugamushi genotypes by intragenic recombination and their potential expansion in endemic areas","volume":"11","author":"Kim","year":"2017","journal-title":"Plos Negl Trop Dis."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1128\/AAC.00551-09","article-title":"Pharmacokinetic-pharmacodynamic modeling of alpha interferon response induced by a Toll-like 7 receptor agonist in mice","volume":"54","author":"Benson","year":"2010","journal-title":"Antimicrob Agents Chemother."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.1128\/IAI.01564-13","article-title":"Type I interferons promote severe disease in a mouse model of lethal ehrlichiosis","volume":"82","author":"Zhang","year":"2014","journal-title":"Infect Immun."},{"key":"B50","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/j.ajpath.2014.10.005","article-title":"Type I interferon contributes to noncanonical inflammasome activation, mediates immunopathology, and impairs protective immunity during fatal infection with lipopolysaccharide-negative ehrlichiae","volume":"185","author":"Yang","year":"2015","journal-title":"Am J Pathol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"5088","DOI":"10.4049\/jimmunol.1401381","article-title":"Stat1 negatively regulates immune-mediated injury with Anaplasma phagocytophilum infection","volume":"193","author":"Choi","year":"2014","journal-title":"J Immunol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"4642","DOI":"10.1128\/IAI.00629-08","article-title":"Type I interferon signaling exacerbates Chlamydia muridarum genital infection in a murine model","volume":"76","author":"Nagarajan","year":"2008","journal-title":"Infect Immun."},{"key":"B53","doi-asserted-by":"publisher","first-page":"e23135","DOI":"10.1371\/journal.pone.0023135","article-title":"MyD88 and STING signaling pathways are required for IRF3-mediated IFN-beta induction in response to Brucella abortus infection","volume":"6","author":"de","year":"2011","journal-title":"PLoS ONE"},{"key":"B54","doi-asserted-by":"publisher","first-page":"e0004991","DOI":"10.1371\/journal.pntd.0004991","article-title":"Protective and Pathogenic Roles of CD8+ T Lymphocytes in Murine Orientia tsutsugamushi Infection","volume":"10","author":"Hauptmann","year":"2016","journal-title":"PLoS Negl Trop Dis."},{"key":"B55","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1084\/jem.20060045","article-title":"Lymphocytes are detrimental during the early innate immune response against Listeria monocytogenes","volume":"203","author":"Carrero","year":"2006","journal-title":"J Exp Med."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.4049\/jimmunol.1502481","article-title":"IL-10 regulates memory T cell development and the balance between Th1 and follicular Th cell responses during an acute viral infection","volume":"197","author":"Tian","year":"2016","journal-title":"J Immunol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"4520","DOI":"10.4049\/jimmunol.179.7.4520","article-title":"Pathogen-specific CD8 T cell responses are directly inhibited by IL-10","volume":"179","author":"Biswas","year":"2007","journal-title":"J Immunol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"2838","DOI":"10.4049\/jimmunol.1501923","article-title":"Differential production of type I IFN determines the reciprocal levels of IL-10 and proinflammatory cytokines produced by C57BL\/6 and BALB\/c macrophages","volume":"197","author":"Howes","year":"2016","journal-title":"J Immunol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"e0004884","DOI":"10.1371\/journal.pntd.0004884","article-title":"An intradermal inoculation mouse model for immunological investigations of acute scrub typhus and persistent infection","volume":"10","author":"Soong","year":"2016","journal-title":"PLoS Negl Trop Dis."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1016\/j.jid.2015.11.034","article-title":"Cross-regulation of proinflammatory cytokines by interleukin-10 and miR-155 in Orientia tsutsugamushi-infected human macrophages prevents cytokine storm","volume":"136","author":"Tsai","year":"2016","journal-title":"J Invest Dermatol."}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2018.02022\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,8]],"date-time":"2020-11-08T21:20:30Z","timestamp":1604870430000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2018.02022\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,4]]},"references-count":60,"alternative-id":["10.3389\/fimmu.2018.02022"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2018.02022","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,4]]},"article-number":"2022"}}