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

Autor(es)

de Carvalho, Gabriel Costa ^{[1, 2]} ; Borget, Marie-Yolande ^[1] ; Bernier, Stephane ^[1] ; Garneau, Daniel ^[1] ; da Silva Duarte, Alberto Jose ^[2] ; Dumais, Nancy ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sherbrooke, Fac Sci, Dept Biol, 2500 Boul Univ, Sherbrooke, PQ J1K 2R1 - Canada

^[2] Univ Sao Paulo, Inst Trop Med, Med Sch, Dept Dermatol, Lab Dermatol & Immunodeficiencies, LIM 56, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Immunobiology; v. 224, n. 6, p. 792-803, NOV 2019.
• Citações Web of Science: 0

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. (AU)

• Processo FAPESP: 17/22539-0 - Efeito do DAMP HMGB-1 e receptor RAGE na transmigração endotelial de monócitos infectados pelo Zika vírus
• Beneficiário: Gabriel Costa de Carvalho
• Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 16/08061-7 - Efeito do DAMP HMGB-1 e receptor RAGE na transmigração endotelial de monócitos infectados pelo Zika vírus
• Beneficiário: Gabriel Costa de Carvalho
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado