title: Expression of neuronal CXCL10 induced by rabies virus infection initiates infiltration of inflammatory cells, production of chemokines and cytokines, and enhancement of blood-brain barrier permeability.
abstract: It has been shown that enhancement of blood-brain barrier (BBB) permeability is modulated by the expression of chemokines/cytokines and reduction of tight junction (TJ) proteins in the brains of mice infected with rabies virus (RABV). Since CXCL10 was found to be the most highly expressed chemokine, its temporal and spatial expression were determined in the present study. The expression of the chemokine CXCL10 was initially detected in neurons as early as 3 days postinfection (p.i.) in the brains of RABV-infected mice, after which it was detected in microglia (6 days p.i.) and astrocytes (9 days p.i.). Neutralization of CXCL10 by treatment with anti-CXCL10 antibodies reduced gamma interferon (IFN-γ) production and Th17 cell infiltration, as well as restoring TJ protein expression and BBB integrity. Together, these data suggest that it is the neuronal CXCL10 that initiates the cascade that leads to the activation of microglia/astrocytes, infiltration of inflammatory cells, expression of chemokines/cytokines, reduction of TJ protein expression, and enhancement of the BBB permeability.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Chai
authors.affiliation: Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Ruiping
authors.initials: R
authors.lastname: She
authors.affiliation: Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA zhenfu@uga.edu.
authors.forename: Zhen F
authors.initials: ZF
authors.lastname: Fu
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D054357:Chemokine CXCL10 / Q000096:biosynthesis*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D007962:Leukocytes / Q000276:immunology*; D008813:Mice, Inbred ICR; D009474:Neurons / Q000276:immunology / Q000821:virology*; D010539:Permeability; D011818:Rabies / Q000276:immunology*; D011820:Rabies virus / Q000276:immunology* / Q000502:physiology; D062725:Tight Junction Proteins / Q000096:biosynthesis; D013997:Time Factors
chemical_list: D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D016207:Cytokines; D062725:Tight Junction Proteins