{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T12:27:26Z","timestamp":1785932846854,"version":"3.56.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2006,9,1]],"date-time":"2006-09-01T00:00:00Z","timestamp":1157068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>What mechanism that determines microglia accomplishing destructive or constructive role in CNS remains nebulous. We report here that intracranial priming and rechallenging with Toxoplasma gondii in mice elicit neurotoxic CCR9+Irg1+ (immunoresponsive gene 1) microglia, which render resistance to apoptosis and produce a high level of TNF-\u03b1; priming and rechallenging with lymphocytic choriomeningitis virus elicit neurosupportive CXCR3+Irg1\u2212 microglia, which are sensitive to apoptosis and produce a high level of IL-10 and TGF-\u03b2. Administration of CCR9 and\/or Irg1 small interfering RNA alters the frequency and functional profiles of neurotoxic CCR9+Irg1+ and neurosupportive CXCR3+Irg1\u2212 microglia in vivo. Moreover, by using a series of different neurotropic pathogens, including intracellular parasites, chronic virus, bacteria, toxic substances, and CNS injury to intracranially prime and subsequent rechallenge mice, the bi-directional elicitation of microglia has been confirmed as neurotoxic CCR9+Irg1+ and neurosupportive CXCR3+Irg1\u2212 cells in these mouse models. These data suggest that there exist two different types of microglia, providing with a novel insight into microglial involvement in neurodegenerative and neuroinflammatory pathogenesis such as Alzheimer\u2019s disease and AIDS dementia.<\/jats:p>","DOI":"10.4049\/jimmunol.177.6.3644","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:17:50Z","timestamp":1397848670000},"page":"3644-3656","source":"Crossref","is-referenced-by-count":57,"title":["Different Neurotropic Pathogens Elicit Neurotoxic CCR9- or Neurosupportive CXCR3-Expressing Microglia"],"prefix":"10.1093","volume":"177","author":[{"given":"He","family":"Li","sequence":"first","affiliation":[{"name":"Department of Immunology, Institute of Allergy and Immune-Related Diseases, Wuhan University School of Medicine , Wuhan ,","place":["People\u2019s Republic of China"]},{"name":"Department of Parasitology, Institute of Allergy and Immune-Related Diseases, Wuhan University School of Medicine , Wuhan ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Gang","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Allergy and Immune-Related Diseases, Wuhan University School of Medicine , Wuhan ,","place":["People\u2019s Republic of China"]},{"name":"Laboratories of Neuroscience, Wuhan University School of Medicine , Wuhan ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Yuling","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Allergy and Immune-Related Diseases, Wuhan University School of Medicine , Wuhan ,","place":["People\u2019s Republic of China"]},{"name":"Laboratories of Neuroscience, Wuhan University School of Medicine , Wuhan ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xie","family":"Luokun","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Allergy and Immune-Related Diseases, Wuhan University School of Medicine , Wuhan ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Jie","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Allergy and Immune-Related Diseases, Wuhan University School of Medicine , Wuhan ,","place":["People\u2019s Republic of China"]},{"name":"The State Key Laboratory of Molecular Biology and Neuroscience, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science , Shanghai ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Hao","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan ,","place":["People\u2019s Republic of China"]},{"name":"Key Laboratory of Colloid, Interface Science and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences , Beijing ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Chunsong","sequence":"additional","affiliation":[{"name":"Department of Immunology, College of Basic Medical Sciences, Anhui Medical University , Hefei ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Junyan","sequence":"additional","affiliation":[{"name":"Allergy and Clinical Immunology, Center for Medical Research, Wuhan University School of Medicine , Wuhan ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Mingshen","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Institute of Allergy and Immune-Related Diseases, Wuhan University School of Medicine , Wuhan ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Youxin","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Molecular Biology and Neuroscience, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science , Shanghai ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gong","family":"Feili","sequence":"additional","affiliation":[{"name":"Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology , Wuhan ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Boquan","sequence":"additional","affiliation":[{"name":"Department of Immunology, Fourth Military Medical University , Xian ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tan","family":"Jinquan","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Allergy and Immune-Related Diseases, Wuhan University School of Medicine , Wuhan ,","place":["People\u2019s Republic of China"]},{"name":"Laboratories of Neuroscience, Wuhan University School of Medicine , Wuhan ,","place":["People\u2019s Republic of China"]},{"name":"Allergy and Clinical Immunology, Center for Medical Research, Wuhan University School of Medicine , Wuhan ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,9,15]]},"reference":[{"key":"2026020213060134700_R1","first-page":"338","volume-title":"N. Engl. J. Med.","year":"2000"},{"key":"2026020213060134700_R2","first-page":"563","volume-title":"Prog. Neurobiol.","year":"1999"},{"key":"2026020213060134700_R3","first-page":"2717","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020213060134700_R4","first-page":"312","volume-title":"Trends Neurosci.","year":"1996"},{"key":"2026020213060134700_R5","first-page":"1","volume-title":"J. Neurosci. Res.","year":"1999"},{"key":"2026020213060134700_R6","first-page":"7922","volume-title":"J. Neurosci.","year":"2003"},{"key":"2026020213060134700_R7","first-page":"2667","volume-title":"J. Immunol.","year":"1998"},{"key":"2026020213060134700_R8","first-page":"8500","volume-title":"J. Neurosci.","year":"2004"},{"key":"2026020213060134700_R9","first-page":"7579","volume-title":"Cancer Res.","year":"2004"},{"key":"2026020213060134700_R10","first-page":"263","volume-title":"Immunogenetics","year":"1995"},{"key":"2026020213060134700_R11","first-page":"5623","volume-title":"Endocrinology","year":"2003"},{"key":"2026020213060134700_R12","first-page":"2081","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020213060134700_R13","first-page":"411","volume-title":"Virology","year":"2000"},{"key":"2026020213060134700_R14","first-page":"521","volume-title":"J. Exp. Med.","year":"1984"},{"key":"2026020213060134700_R15","first-page":"8056","volume-title":"J. Virol.","year":"1994"},{"key":"2026020213060134700_R16","first-page":"5802","volume-title":"J. Immunol.","year":"2003"},{"key":"2026020213060134700_R17","first-page":"3484","volume-title":"J. Neurosci.","year":"2002"},{"key":"2026020213060134700_R18","first-page":"9879","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1999"},{"key":"2026020213060134700_R19","first-page":"6015","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1998"},{"key":"2026020213060134700_R20","first-page":"9070","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2000"},{"key":"2026020213060134700_R21","first-page":"969","volume-title":"J. Exp. Med.","year":"1997"},{"key":"2026020213060134700_R22","first-page":"195","volume-title":"J. Immunol. Methods","year":"1997"},{"key":"2026020213060134700_R23","first-page":"30142","volume-title":"J. Biol. Chem.","year":"2001"},{"key":"2026020213060134700_R24","first-page":"3365","volume-title":"Cancer Res.","year":"2004"},{"key":"2026020213060134700_R25","first-page":"2744","volume-title":"J. Immunol.","year":"2004"},{"key":"2026020213060134700_R26","first-page":"219","volume-title":"Glia","year":"2003"},{"key":"2026020213060134700_R27","first-page":"261","volume-title":"Brain Res. Brain Res. Rev.","year":"2004"},{"key":"2026020213060134700_R28","first-page":"1240","volume-title":"J. Immunol.","year":"2004"},{"key":"2026020213060134700_R29","first-page":"156","volume-title":"Glia","year":"2001"},{"key":"2026020213060134700_R30","first-page":"2496","volume-title":"J. Immunol.","year":"2003"},{"key":"2026020213060134700_R31","first-page":"130","volume-title":"J. Mol. Med.","year":"1997"},{"key":"2026020213060134700_R32","first-page":"1356","volume-title":"Nat. Med.","year":"2001"},{"key":"2026020213060134700_R33","first-page":"140","volume-title":"Glia","year":"2002"},{"key":"2026020213060134700_R34","first-page":"42","volume-title":"Brain Res. Rev.","year":"1999"},{"key":"2026020213060134700_R35","first-page":"3504","volume-title":"J. Immunol.","year":"2004"},{"key":"2026020213060134700_R36","first-page":"133","volume-title":"Glia","year":"2002"},{"key":"2026020213060134700_R37","first-page":"134","volume-title":"J. Immunol.","year":"2002"},{"key":"2026020213060134700_R38","first-page":"850","volume-title":"Blood","year":"2001"},{"key":"2026020213060134700_R39","first-page":"88","volume-title":"Nature","year":"2003"},{"key":"2026020213060134700_R40","first-page":"159","volume-title":"J. Immunol.","year":"2003"},{"key":"2026020213060134700_R41","first-page":"388","volume-title":"J. Leukocyte Biol.","year":"2004"},{"key":"2026020213060134700_R42","first-page":"1","volume-title":"J. Neurosci. Res.","year":"2004"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/177\/6\/3644\/62650438\/zim01806003644.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/177\/6\/3644\/62650438\/zim01806003644.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T18:08:58Z","timestamp":1770055738000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/177\/6\/3644\/8037451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,9]]},"references-count":42,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2006,9,15]]},"published-print":{"date-parts":[[2006,9,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.177.6.3644","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2006,9]]},"published":{"date-parts":[[2006,9]]}}}