Inflammatory monocytes damage the hippocampus during acute picornavirus infection of the brain
<p>Abstract</p> <p>Background</p> <p>Neuropathology caused by acute viral infection of the brain is associated with the development of persistent neurological deficits. Identification of the immune effectors responsible for injuring the brain during acute infection is n...
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doaj-c168616a58e743f0a47e6c2c1dc50e082020-11-25T00:45:26ZengBMCJournal of Neuroinflammation1742-20942012-03-01915010.1186/1742-2094-9-50Inflammatory monocytes damage the hippocampus during acute picornavirus infection of the brainHowe Charles LLaFrance-Corey Reghann GSundsbak Rhianna SLaFrance Stephanie J<p>Abstract</p> <p>Background</p> <p>Neuropathology caused by acute viral infection of the brain is associated with the development of persistent neurological deficits. Identification of the immune effectors responsible for injuring the brain during acute infection is necessary for the development of therapeutic strategies that reduce neuropathology but maintain immune control of the virus.</p> <p>Methods</p> <p>The identity of brain-infiltrating leukocytes was determined using microscopy and flow cytometry at several acute time points following intracranial infection of mice with the Theiler's murine encephalomyelitis virus. Behavioral consequences of immune cell depletion were assessed by Morris water maze.</p> <p>Results</p> <p>Inflammatory monocytes, defined as CD45<sup>hi</sup>CD11b<sup>++</sup>F4/80<sup>+</sup>Gr1<sup>+</sup>1A8<sup>-</sup>, and neutrophils, defined as CD45<sup>hi</sup>CD11b<sup>+++</sup>F4/80<sup>-</sup>Gr1<sup>+</sup>1A8<sup>+</sup>, were found in the brain at 12 h after infection. Flow cytometry of brain-infiltrating leukocytes collected from LysM: GFP reporter mice confirmed the identification of neutrophils and inflammatory monocytes in the brain. Microscopy of sections from infected LysM:GFP mice showed that infiltrating cells were concentrated in the hippocampal formation. Immunostaining confirmed that neutrophils and inflammatory monocytes were localized to the hippocampal formation at 12 h after infection. Immunodepletion of inflammatory monocytes and neutrophils but not of neutrophils only resulted in preservation of hippocampal neurons. Immunodepletion of inflammatory monocytes also preserved cognitive function as assessed by the Morris water maze.</p> <p>Conclusions</p> <p>Neutrophils and inflammatory monocytes rapidly and robustly responded to Theiler's virus infection by infiltrating the brain. Inflammatory monocytes preceded neutrophils, but both cell types were present in the hippocampal formation at a timepoint that is consistent with a role in triggering hippocampal pathology. Depletion of inflammatory monocytes and neutrophils with the Gr1 antibody resulted in hippocampal neuroprotection and preservation of cognitive function. Specific depletion of neutrophils with the 1A8 antibody failed to preserve neurons, suggesting that inflammatory monocytes are the key effectors of brain injury during acute picornavirus infection of the brain. These effector cells may be important therapeutic targets for immunomodulatory or immunosuppressive therapies aimed at reducing or preventing central nervous system pathology associated with acute viral infection.</p> http://www.jneuroinflammation.com/content/9/1/501A8alveusbrain-infiltrating leukocytesCD11bGr1hippocampusinflammatory monocytemacrophageneutrophilLysM:GFP reporter mouseLy6CLy6GTheiler's virus |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Howe Charles L LaFrance-Corey Reghann G Sundsbak Rhianna S LaFrance Stephanie J |
spellingShingle |
Howe Charles L LaFrance-Corey Reghann G Sundsbak Rhianna S LaFrance Stephanie J Inflammatory monocytes damage the hippocampus during acute picornavirus infection of the brain Journal of Neuroinflammation 1A8 alveus brain-infiltrating leukocytes CD11b Gr1 hippocampus inflammatory monocyte macrophage neutrophil LysM:GFP reporter mouse Ly6C Ly6G Theiler's virus |
author_facet |
Howe Charles L LaFrance-Corey Reghann G Sundsbak Rhianna S LaFrance Stephanie J |
author_sort |
Howe Charles L |
title |
Inflammatory monocytes damage the hippocampus during acute picornavirus infection of the brain |
title_short |
Inflammatory monocytes damage the hippocampus during acute picornavirus infection of the brain |
title_full |
Inflammatory monocytes damage the hippocampus during acute picornavirus infection of the brain |
title_fullStr |
Inflammatory monocytes damage the hippocampus during acute picornavirus infection of the brain |
title_full_unstemmed |
Inflammatory monocytes damage the hippocampus during acute picornavirus infection of the brain |
title_sort |
inflammatory monocytes damage the hippocampus during acute picornavirus infection of the brain |
publisher |
BMC |
series |
Journal of Neuroinflammation |
issn |
1742-2094 |
publishDate |
2012-03-01 |
description |
<p>Abstract</p> <p>Background</p> <p>Neuropathology caused by acute viral infection of the brain is associated with the development of persistent neurological deficits. Identification of the immune effectors responsible for injuring the brain during acute infection is necessary for the development of therapeutic strategies that reduce neuropathology but maintain immune control of the virus.</p> <p>Methods</p> <p>The identity of brain-infiltrating leukocytes was determined using microscopy and flow cytometry at several acute time points following intracranial infection of mice with the Theiler's murine encephalomyelitis virus. Behavioral consequences of immune cell depletion were assessed by Morris water maze.</p> <p>Results</p> <p>Inflammatory monocytes, defined as CD45<sup>hi</sup>CD11b<sup>++</sup>F4/80<sup>+</sup>Gr1<sup>+</sup>1A8<sup>-</sup>, and neutrophils, defined as CD45<sup>hi</sup>CD11b<sup>+++</sup>F4/80<sup>-</sup>Gr1<sup>+</sup>1A8<sup>+</sup>, were found in the brain at 12 h after infection. Flow cytometry of brain-infiltrating leukocytes collected from LysM: GFP reporter mice confirmed the identification of neutrophils and inflammatory monocytes in the brain. Microscopy of sections from infected LysM:GFP mice showed that infiltrating cells were concentrated in the hippocampal formation. Immunostaining confirmed that neutrophils and inflammatory monocytes were localized to the hippocampal formation at 12 h after infection. Immunodepletion of inflammatory monocytes and neutrophils but not of neutrophils only resulted in preservation of hippocampal neurons. Immunodepletion of inflammatory monocytes also preserved cognitive function as assessed by the Morris water maze.</p> <p>Conclusions</p> <p>Neutrophils and inflammatory monocytes rapidly and robustly responded to Theiler's virus infection by infiltrating the brain. Inflammatory monocytes preceded neutrophils, but both cell types were present in the hippocampal formation at a timepoint that is consistent with a role in triggering hippocampal pathology. Depletion of inflammatory monocytes and neutrophils with the Gr1 antibody resulted in hippocampal neuroprotection and preservation of cognitive function. Specific depletion of neutrophils with the 1A8 antibody failed to preserve neurons, suggesting that inflammatory monocytes are the key effectors of brain injury during acute picornavirus infection of the brain. These effector cells may be important therapeutic targets for immunomodulatory or immunosuppressive therapies aimed at reducing or preventing central nervous system pathology associated with acute viral infection.</p> |
topic |
1A8 alveus brain-infiltrating leukocytes CD11b Gr1 hippocampus inflammatory monocyte macrophage neutrophil LysM:GFP reporter mouse Ly6C Ly6G Theiler's virus |
url |
http://www.jneuroinflammation.com/content/9/1/50 |
work_keys_str_mv |
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