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

Lymphocytic choriomeningitis virus infection of the mouse central nervous system (CNS) elicits fatal immunopathology through blood-brain barrier breakdown and convulsive seizures. Although lymphocytic-choriomeningitis-virus-specific cytotoxic T lymphocytes (CTLs) are essential for disease, their mec...

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Main Authors: Kim, J, Kang, S, Dustin, M, McGavern, D
Format: Journal article
Language:English
Published: 2009
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author Kim, J
Kang, S
Dustin, M
McGavern, D
author_facet Kim, J
Kang, S
Dustin, M
McGavern, D
author_sort Kim, J
collection OXFORD
description Lymphocytic choriomeningitis virus infection of the mouse central nervous system (CNS) elicits fatal immunopathology through blood-brain barrier breakdown and convulsive seizures. Although lymphocytic-choriomeningitis-virus-specific cytotoxic T lymphocytes (CTLs) are essential for disease, 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.
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spelling oxford-uuid:4a141920-12fc-42cc-87e0-d5ceaca663f02022-03-26T15:35:28ZMyelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4a141920-12fc-42cc-87e0-d5ceaca663f0EnglishSymplectic Elements at Oxford2009Kim, JKang, SDustin, MMcGavern, DLymphocytic choriomeningitis virus infection of the mouse central nervous system (CNS) elicits fatal immunopathology through blood-brain barrier breakdown and convulsive seizures. Although lymphocytic-choriomeningitis-virus-specific cytotoxic T lymphocytes (CTLs) are essential for disease, 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.
spellingShingle Kim, J
Kang, S
Dustin, M
McGavern, D
Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis.
title Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis.
title_full Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis.
title_fullStr Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis.
title_full_unstemmed Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis.
title_short Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis.
title_sort myelomonocytic cell recruitment causes fatal cns vascular injury during acute viral meningitis
work_keys_str_mv AT kimj myelomonocyticcellrecruitmentcausesfatalcnsvascularinjuryduringacuteviralmeningitis
AT kangs myelomonocyticcellrecruitmentcausesfatalcnsvascularinjuryduringacuteviralmeningitis
AT dustinm myelomonocyticcellrecruitmentcausesfatalcnsvascularinjuryduringacuteviralmeningitis
AT mcgavernd myelomonocyticcellrecruitmentcausesfatalcnsvascularinjuryduringacuteviralmeningitis