RAGE and CCR7 mediate the transmigration of Zika-infected monocytes through the blood-brain barrier

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Arquivos
art_CARVALHO_RAGE_and_CCR7_mediate_the_transmigration_of_Zikainfected_2019.PDF (2.21 MB)
Citações na Scopus
21
Tipo de produção
article
Data de publicação
2019
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER GMBH
Autores
BORGET, Marie-Yolande
BERNIER, Stephane
GARNEAU, Daniel
DUMAIS, Nancy
Citação
IMMUNOBIOLOGY, v.224, n.6, p.792-803, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Details of the ""Trojan Horse"" mechanism by which Zika virus (ZIKV) crosses the blood-brain barrier (BBB) remain unclear. However, the migration of ZIKV-infected monocytes to the brain is thought to be dependent on both pattern-recognition and chemokine receptors. In this study, we investigated whether the migration of ZIKV-infected MonoMac-1 (MM-1) cells through the BBB is dependent on chemokine receptor 7 (CCR7) and receptor for advanced glycation end (RAGE); we also determined whether high mobility group box protein 1 (HMGB1) could facilitate the permeabilization of endothelial cells. We demonstrated that ZIKV infects MM-1 cells, leading to milieu accumulation of HMGB1. Our results suggest that HMGB1 is involved in the dysregulation of primary human brain microvascular endothelial cell junction markers. Our results also indicate that the migration of ZIKV-infected monocytes is dependent on chemokine ligand 19 (CCL19), the natural ligand of CCR7, in conditions recapitulating inflammation. RAGE-dependent migration of ZIKV-infected cells declined during transmigration assays in the presence of RAGE receptor antagonist FPS-ZM1. Understanding the molecular role of monocyte trafficking during ZIKV infections could facilitate the development of new therapeutic strategies to prevent the deleterious consequences of ZIKV neuroinfection.
Palavras-chave
Zika virus, Monocytes, Blood-brain barrier, RAGE, CCR7, HMGB1
URI
https://observatorio.fm.usp.br/handle/OPI/34560
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/56
Artigos e Materiais de Revistas Científicas - ODS/03