title: Different neurotropic pathogens elicit neurotoxic CCR9- or neurosupportive CXCR3-expressing microglia.
abstract: 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-alpha; priming and rechallenging with lymphocytic choriomeningitis virus elicit neurosupportive CXCR3+ Irg1- microglia, which are sensitive to apoptosis and produce a high level of IL-10 and TGF-beta. Administration of CCR9 and/or Irg1 small interfering RNA alters the frequency and functional profiles of neurotoxic CCR9+ Irg1+ and neurosupportive CXCR3+ Irg1- 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- 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's disease and AIDS dementia.
authors.affiliation: Department of Immunology, Institute of Allergy and Immune-Related Diseases, Center for Medical Research, Wuhan University School of Medicine, Wuhan's People's Republic of China.
authors.forename: He
authors.initials: H
authors.lastname: Li
authors.forename: Zhou
authors.initials: Z
authors.lastname: Gang
authors.forename: He
authors.initials: H
authors.lastname: Yuling
authors.forename: Xie
authors.initials: X
authors.lastname: Luokun
authors.forename: Xiong
authors.initials: X
authors.lastname: Jie
authors.forename: Lei
authors.initials: L
authors.lastname: Hao
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Hu
authors.initials: H
authors.lastname: Chunsong
authors.forename: Liu
authors.initials: L
authors.lastname: Junyan
authors.forename: Jiang
authors.initials: J
authors.lastname: Mingshen
authors.forename: Jin
authors.initials: J
authors.lastname: Youxin
authors.forename: Gong
authors.initials: G
authors.lastname: Feili
authors.forename: Jin
authors.initials: J
authors.lastname: Boquan
authors.forename: Tan
authors.initials: T
authors.lastname: Jinquan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology / Q000469:parasitology* / Q000473:pathology / Q000821:virology*; D009498:Neurotoxins / Q000096:biosynthesis* / Q000235:genetics / Q000633:toxicity*; D054388:Receptors, CCR; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology / Q000472:pathogenicity*; D014123:Toxoplasmosis / Q000276:immunology / Q000378:metabolism / Q000469:parasitology
chemical_list: C119309:CC chemokine receptor 9; C515188:Cxcr3 protein, mouse; D009498:Neurotoxins; D054388:Receptors, CCR; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine