Defective inflammatory monocyte development in IRF8-deficient mice abrogates migration to the West Nile virus-infected brain.
J Innate Immun
; 7(1): 102-12, 2015.
Article
em En
| MEDLINE
| ID: mdl-25277331
ABSTRACT
IRF8 (interferon-regulatory factor-8) plays a critical role in regulating myeloid cell differentiation. However, the role of this transcription factor in the development of Ly6C+ inflammatory monocytes and their migration to the infected brain has not been examined. We have previously shown that West Nile virus (WNV) infection of wild-type (WT) mice triggers a significant increase in numbers of Ly6C+ monocytes in the bone marrow. These cells traffic via the blood to the infected brain, where they give rise to proinflammatory macrophages. Here, we show that WNV-infected IRF8-deficient (IRF8-/-) mice had significantly reduced numbers of Ly6C+ monocytes in the periphery, with few of these cells found in the blood. Furthermore, low numbers of inflammatory monocyte-derived macrophages were observed in the brains of IRF8-/- mice throughout infection. Adoptive transfer of IRF8-/- Ly6C+ monocytes demonstrated that these cells were intrinsically unable to traffic to the inflamed brain. Low expression of the chemokine receptor CCR2 and integrin VLA-4 by IRF8-/- monocytes likely contributed to this defect, as the interactions between these proteins and their ligands are critical for monocyte egress and migration to inflammatory foci. These data highlight a critical role for IRF8 in inflammatory monocyte differentiation and migration during WNV infection.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Febre do Nilo Ocidental
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Vírus do Nilo Ocidental
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Encéfalo
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Monócitos
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Movimento Celular
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Fatores Reguladores de Interferon
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article