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Intracerebral immune complex formation induces inflammation in the brain that depends on Fc receptor interaction

Intracerebral immune complex formation induces inflammation in the brain that depends on Fc receptor interaction
Intracerebral immune complex formation induces inflammation in the brain that depends on Fc receptor interaction
Abstract In this study, we investigate the underlying mechanisms of antibody-mediated inflammation in the brain. We show that immune complexes formed in the brain parenchyma generate a robust and long-lasting inflammatory response, characterized by increased expression of the microglia markers CD11b, CD68 and FcRII/III, but no neutrophil recruitment. In addition to these histological changes, we observed transient behavioural changes that coincided with the inflammatory response in the brain. The inflammatory and behavioural changes were absent in Fc-gamma chain (Fcc)-deficient mice, while C1q-deficient mice were not different from wild-type mice. We conclude that, in the presence of antigen, antibodies can lead to a local immune complex-mediated inflammatory reaction in the brain parenchyma and indirectly induce neuronal tissue damage through recruitment and activation of microglia via Fcc receptors. These observations may have important implications for the development of therapeutic antibodies directed against neuronal antigens used for therapeutic intervention in neurological diseases.
0001-6322
479-490
Teeling, Jessica L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Carare, Roxana O.
0478c197-b0c1-4206-acae-54e88c8f21fa
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Perry, V. Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Teeling, Jessica L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Carare, Roxana O.
0478c197-b0c1-4206-acae-54e88c8f21fa
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Perry, V. Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4

Teeling, Jessica L., Carare, Roxana O., Glennie, Martin J. and Perry, V. Hugh (2012) Intracerebral immune complex formation induces inflammation in the brain that depends on Fc receptor interaction. Acta Neuropathologica, 124 (4), 479-490. (doi:10.1007/s00401-012-0995-3).

Record type: Article

Abstract

Abstract In this study, we investigate the underlying mechanisms of antibody-mediated inflammation in the brain. We show that immune complexes formed in the brain parenchyma generate a robust and long-lasting inflammatory response, characterized by increased expression of the microglia markers CD11b, CD68 and FcRII/III, but no neutrophil recruitment. In addition to these histological changes, we observed transient behavioural changes that coincided with the inflammatory response in the brain. The inflammatory and behavioural changes were absent in Fc-gamma chain (Fcc)-deficient mice, while C1q-deficient mice were not different from wild-type mice. We conclude that, in the presence of antigen, antibodies can lead to a local immune complex-mediated inflammatory reaction in the brain parenchyma and indirectly induce neuronal tissue damage through recruitment and activation of microglia via Fcc receptors. These observations may have important implications for the development of therapeutic antibodies directed against neuronal antigens used for therapeutic intervention in neurological diseases.

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e-pub ahead of print date: 18 May 2012
Published date: October 2012
Organisations: Faculty of Natural and Environmental Sciences, Faculty of Medicine, Cancer Sciences, Centre for Biological Sciences

Identifiers

Local EPrints ID: 339169
URI: https://eprints.soton.ac.uk/id/eprint/339169
ISSN: 0001-6322
PURE UUID: 05a01c7f-7cbb-4a9b-b9c6-505708b996c3
ORCID for Jessica L. Teeling: ORCID iD orcid.org/0000-0003-4004-7391

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Date deposited: 24 May 2012 12:50
Last modified: 19 Jun 2019 00:35

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Author: V. Hugh Perry

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