Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis

被引:264
作者
Kim, Jiyun V. [1 ]
Kang, Silvia S. [2 ]
Dustin, Michael L. [1 ]
McGavern, Dorian B. [2 ]
机构
[1] NYU, Sch Med, Helen L & Martin S Kimmel Ctr Biol & Med, Skirball Inst Biomol Med,Program Mol Pathogenesis, New York, NY 10016 USA
[2] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA
基金
美国国家卫生研究院;
关键词
BLOOD-BRAIN-BARRIER; MURINE LYMPHOCYTIC CHORIOMENINGITIS; CENTRAL-NERVOUS-SYSTEM; VIRUS-INFECTION; T-CELLS; ANTICONVULSANT PROLONGATION; CHEMOKINE RECEPTOR; HOST-DEFENSE; MICE; PERMEABILITY;
D O I
10.1038/nature07591
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Lymphocytic choriomeningitis virus(1) infection of the mouse central nervous system (CNS) elicits fatal immunopathology through blood - brain barrier breakdown(2) and convulsive seizures(3). Although lymphocytic- choriomeningitis- virus- specific cytotoxic T lymphocytes ( CTLs) are essential for disease(4), their mechanism of action is not known. To gain insights into disease pathogenesis, we observed the dynamics of immune cells in the meninges by two-photon microscopy. Here we report visualization of motile CTLs and massive secondary recruitment of pathogenic monocytes and neutrophils that were required for vascular leakage and acute lethality. CTLs expressed multiple chemoattractants capable of recruiting myelomonocytic cells. We conclude that a CD8(+) T- cell- dependent disorder can proceed in the absence of direct T- cell effector mechanisms and rely instead on CTL- recruited myelomonocytic cells.
引用
收藏
页码:191 / U85
页数:7
相关论文
共 36 条
[1]   Transendothelial migration of CD16+ monocytes in response to fractalkine under constitutive and inflammatory conditions [J].
Ancuta, P ;
Moses, A ;
Gabuzda, D .
IMMUNOBIOLOGY, 2004, 209 (1-2) :11-20
[2]   BREAKDOWN OF BLOOD-BRAIN-BARRIER FUNCTION IN THE MURINE LYMPHOCYTIC CHORIOMENINGITIS VIRUS-INFECTION MEDIATED BY VIRUS-SPECIFIC CD8+T CELLS [J].
ANDERSEN, IH ;
MARKER, O ;
THOMSEN, AR .
JOURNAL OF NEUROIMMUNOLOGY, 1991, 31 (02) :155-163
[3]   Chemokine gene expression in the brains of mice with lymphocytic choriomeningitis [J].
Asensio, VC ;
Campbell, IL .
JOURNAL OF VIROLOGY, 1997, 71 (10) :7832-7840
[4]   Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes [J].
Bajenoff, Marc ;
Egen, Jackson G. ;
Koo, Lily Y. ;
Laugier, Jean Pierre ;
Brau, Frederic ;
Glaichenhaus, Nicolas ;
Germain, Ronald N. .
IMMUNITY, 2006, 25 (06) :989-1001
[5]   Protein kinase CO regulates stability of the peripheral adhesion ring junction and contributes to the sensitivity of target cell lysis by CTL [J].
Beal, Allison M. ;
Anikeeva, Nadia ;
Varma, Rajat ;
Cameron, Thomas O. ;
Norris, Philip J. ;
Dustin, Michael L. ;
Sykulev, Yuri .
JOURNAL OF IMMUNOLOGY, 2008, 181 (07) :4815-4824
[6]  
Bjork J, 1982, Agents Actions Suppl, V11, P63
[7]   Cutting edge: Hierarchy of chemokine receptor and TCR signals regulating T cell migration and proliferation [J].
Bromley, SK ;
Peterson, DA ;
Gunn, MD ;
Dustin, ML .
JOURNAL OF IMMUNOLOGY, 2000, 165 (01) :15-19
[8]   ANTICONVULSANT PROLONGATION OF SURVIVAL IN ADULT MURINE LYMPHOCYTIC CHORIOMENINGITIS .1. DRUG-TREATMENT AND VIROLOGIC STUDIES [J].
CAMENGA, DL ;
WALKER, DH ;
MURPHY, FA .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1977, 36 (01) :9-20
[9]   Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d:: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis [J].
Crozat, Karine ;
Hoebe, Kasper ;
Ugolini, Sophie ;
Hong, Nancy A. ;
Janssen, Edith ;
Rutschmann, Sophie ;
Mudd, Suzanne ;
Sovath, Sosathya ;
Vivier, Eric ;
Beutler, Bruce .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (04) :853-863
[10]  
DOHERTY PC, 1990, IMMUNOL TODAY, V11, P55