Peripheral nervous system is injured by neutrophil extracellular traps (NETs) elicited by nonstructural (NS) protein-1 from Zika virus
© 2023 Federation of American Societies for Experimental Biology..
The involvement of innate immune mediators to the Zika virus (ZIKV)-induced neuroinflammation is not yet well known. Here, we investigated whether neutrophil extracellular traps (NETs), which are scaffolds of DNA associated with proteins, have the potential to injure peripheral nervous. The tissue lesions were evaluated after adding NETs to dorsal root ganglia (DRG) explants and to DRG constituent cells or injecting them into mouse sciatic nerves. Identification of NET harmful components was achieved by pharmacological inhibition of NET constituents. We found that ZIKV inoculation into sciatic nerves recruited neutrophils and elicited the production of the cytokines CXCL1 and IL-1β, classical NET inducers, but did not trigger NET formation. ZIKV blocked PMA- and CXCL8-induced NET release, but, in contrast, the ZIKV nonstructural protein (NS)-1 induced NET formation. NET-enriched supernatants were toxic to DRG explants, decreasing neurite area, length, and arborization. NETs were toxic to DRG constituent cells and affected myelinating cells. Myeloperoxidase (MPO) and histones were identified as the harmful component of NETs. NS1 injection into mouse sciatic nerves recruited neutrophils and triggered NET release and caspase-3 activation, events that were also elicited by the injection of purified MPO. In summary, we found that ZIKV NS1 protein induces NET formation, which causes nervous tissue damages. Our findings reveal new mechanisms leading to neuroinflammation by ZIKV.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:37 |
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| Enthalten in: |
FASEB journal : official publication of the Federation of American Societies for Experimental Biology - 37(2023), 9 vom: 20. Sept., Seite e23126 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
de Siqueira Santos, Raphael [VerfasserIn] |
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| Links: |
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| Themen: |
Histones |
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| Anmerkungen: |
Date Completed 21.08.2023 Date Revised 29.08.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1096/fj.202201904R |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360928943 |
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| 100 | 1 | |a de Siqueira Santos, Raphael |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Peripheral nervous system is injured by neutrophil extracellular traps (NETs) elicited by nonstructural (NS) protein-1 from Zika virus |
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| 520 | |a The involvement of innate immune mediators to the Zika virus (ZIKV)-induced neuroinflammation is not yet well known. Here, we investigated whether neutrophil extracellular traps (NETs), which are scaffolds of DNA associated with proteins, have the potential to injure peripheral nervous. The tissue lesions were evaluated after adding NETs to dorsal root ganglia (DRG) explants and to DRG constituent cells or injecting them into mouse sciatic nerves. Identification of NET harmful components was achieved by pharmacological inhibition of NET constituents. We found that ZIKV inoculation into sciatic nerves recruited neutrophils and elicited the production of the cytokines CXCL1 and IL-1β, classical NET inducers, but did not trigger NET formation. ZIKV blocked PMA- and CXCL8-induced NET release, but, in contrast, the ZIKV nonstructural protein (NS)-1 induced NET formation. NET-enriched supernatants were toxic to DRG explants, decreasing neurite area, length, and arborization. NETs were toxic to DRG constituent cells and affected myelinating cells. Myeloperoxidase (MPO) and histones were identified as the harmful component of NETs. NS1 injection into mouse sciatic nerves recruited neutrophils and triggered NET release and caspase-3 activation, events that were also elicited by the injection of purified MPO. In summary, we found that ZIKV NS1 protein induces NET formation, which causes nervous tissue damages. Our findings reveal new mechanisms leading to neuroinflammation by ZIKV | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a NS1 ZIKV protein | |
| 650 | 4 | |a Schwann cells (SC) | |
| 650 | 4 | |a Zika virus (ZIKV) | |
| 650 | 4 | |a histones | |
| 650 | 4 | |a myeloperoxidase | |
| 650 | 4 | |a neutrophil extracellular traps (NETs) | |
| 700 | 1 | |a Rochael, Natalia Cadaxo |e verfasserin |4 aut | |
| 700 | 1 | |a Mattos, Thayana Roberta F |e verfasserin |4 aut | |
| 700 | 1 | |a Fallett E Silva, Matheus Felipe |e verfasserin |4 aut | |
| 700 | 1 | |a Linhares-Lacerda, Leandra |e verfasserin |4 aut | |
| 700 | 1 | |a de Oliveira, Leandro Teixeira |e verfasserin |4 aut | |
| 700 | 1 | |a Cunha, Marcela Sabino |e verfasserin |4 aut | |
| 700 | 1 | |a Mohana-Borges, Ronaldo |e verfasserin |4 aut | |
| 700 | 1 | |a Gomes, Tiago Araujo |e verfasserin |4 aut | |
| 700 | 1 | |a Barbosa-Silva, Maria Carolina |e verfasserin |4 aut | |
| 700 | 1 | |a Maron-Gutierrez, Tatiana |e verfasserin |4 aut | |
| 700 | 1 | |a Foguel, Debora |e verfasserin |4 aut | |
| 700 | 1 | |a Saraiva, Elvira Maria |e verfasserin |4 aut | |
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