{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T01:50:24Z","timestamp":1773798624965,"version":"3.50.1"},"reference-count":60,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,7,12]],"date-time":"2016-07-12T00:00:00Z","timestamp":1468281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2016,10]]},"abstract":"Summary<\/jats:title>Japanese encephalitis virus (JEV<\/jats:styled-content>) is a re\u2010emerging zoonotic flavivirus that poses an increasing threat to global health and welfare due to rapid changes in climate and demography. Although the CCR<\/jats:styled-content>2\u2013CCL<\/jats:styled-content>2 axis plays an important role in trafficking CD<\/jats:styled-content>11b+<\/jats:sup> Ly\u20106Chi<\/jats:sup> monocytes to regulate immunopathological diseases, little is known about their role in monocyte trafficking during viral encephalitis caused by JEV<\/jats:styled-content> infection. Here, we explored the role of CCR<\/jats:styled-content>2 and its ligand CCL<\/jats:styled-content>2 in JE<\/jats:styled-content> caused by JEV<\/jats:styled-content> infection using CCR<\/jats:styled-content>2\u2010 and CCL<\/jats:styled-content>2\u2010ablated murine models. Somewhat surprisingly, the ablation of CCR<\/jats:styled-content>2 and CCL<\/jats:styled-content>2 resulted in starkly contrasting susceptibility to JE<\/jats:styled-content>. CCR<\/jats:styled-content>2 ablation induced enhanced resistance to JE<\/jats:styled-content>, whereas CCL<\/jats:styled-content>2 ablation highly increased susceptibility to JE<\/jats:styled-content>. This contrasting regulation of JE<\/jats:styled-content> progression by CCR<\/jats:styled-content>2 and CCL<\/jats:styled-content>2 was coupled to central nervous system (CNS<\/jats:styled-content>) infiltration of Ly\u20106Chi<\/jats:sup> monocytes and Ly\u20106Ghi<\/jats:sup> granulocytes. There was also enhanced expression of CC<\/jats:styled-content> and CXC<\/jats:styled-content> chemokines in the CNS<\/jats:styled-content> of CCL<\/jats:styled-content>2\u2010ablated mice, which appeared to induce CNS<\/jats:styled-content> infiltration of these cell populations. However, our data revealed that contrasting regulation of JE<\/jats:styled-content> in CCR<\/jats:styled-content>2\u2010 and CCL<\/jats:styled-content>2\u2010ablated mice was unlikely to be mediated by innate natural killer and adaptive T\u2010cell responses. Furthermore, CCL<\/jats:styled-content>2 produced by haematopoietic stem cell\u2010derived leucocytes played a dominant role in CNS<\/jats:styled-content> accumulation of Ly\u20106Chi<\/jats:sup> monocytes in infected bone marrow chimeric models, thereby exacerbating JE<\/jats:styled-content> progression. Collectively, our data indicate that CCL<\/jats:styled-content>2 plays an essential role in conferring protection against JE<\/jats:styled-content> caused by JEV<\/jats:styled-content> infection. In addition, blockage of CCR<\/jats:styled-content>2, but not CCL<\/jats:styled-content>2, will aid in the development of strategies for prophylactics and therapeutics of JE<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/imm.12626","type":"journal-article","created":{"date-parts":[[2016,6,4]],"date-time":"2016-06-04T15:39:23Z","timestamp":1465054763000},"page":"186-203","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["CCL<\/scp>2, but not its receptor, is essential to restrict immune privileged central nervous system\u2010invasion of Japanese encephalitis virus via regulating accumulation of CD<\/scp>11b+<\/sup> Ly\u20106Chi<\/sup> monocytes"],"prefix":"10.1111","volume":"149","author":[{"given":"Jin Hyoung","family":"Kim","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine and Bio\u2010Safety Research Institute Chonbuk National University Iksan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajit Mahadev","family":"Patil","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine and Bio\u2010Safety Research Institute Chonbuk National University Iksan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Young","family":"Choi","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine and Bio\u2010Safety Research Institute Chonbuk National University Iksan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong Bum","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine and Bio\u2010Safety Research Institute Chonbuk National University Iksan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erdenebileg","family":"Uyangaa","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine and Bio\u2010Safety Research Institute Chonbuk National University Iksan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferdaus Mohd Altaf","family":"Hossain","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine and Bio\u2010Safety Research Institute Chonbuk National University Iksan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang\u2010Youel","family":"Park","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine and Bio\u2010Safety Research Institute Chonbuk National University Iksan Korea"},{"name":"Department of Bioactive Material Sciences Graduate School Chonbuk National University Jeonju Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John Hwa","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine and Bio\u2010Safety Research Institute Chonbuk National University Iksan Korea"},{"name":"Department of Bioactive Material Sciences Graduate School Chonbuk National University Jeonju Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koanhoi","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Pusan National University Yangsan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong Kug","family":"Eo","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine and Bio\u2010Safety Research Institute Chonbuk National University Iksan Korea"},{"name":"Department of Bioactive Material Sciences Graduate School Chonbuk National University Jeonju Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,7,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002208"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13365-014-0285-z"},{"key":"e_1_2_9_4_1","first-page":"658","article-title":"Japanese encephalitis surveillance and immunization \u2013 Asia and the Western Pacific, 2012","volume":"62","author":"Centers for Disease Control and Prevention","year":"2013","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000437"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0438-x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00405-3"},{"key":"e_1_2_9_8_1","unstructured":"Center for Disease Control.West Nile activity \u2013 human disease cases reported. 2005\u20132009(2009) Available at:http:\/\/www.cdc.gov\/ncidod\/dvbid\/westnile\/sur&control.htm. 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