Neutrophil Virucidal Activity Against SARS-CoV-2 Is Mediated by Neutrophil Extracellular Traps

Autor(es):Mostrar menos -

Almeida, Cicero Jose Luiz dos Ramos ; Veras, Flavio Protasio ; Paiva, Isadora Marques ; Schneider, Ayda Henriques ; Silva, Juliana da Costa ; Gomes, Giovanni Freitas ; Costa, Victor Ferreira ; Silva, Bruna Manuella Souza ; Caetite, Diego Brito ; Silva, Camila Meirelles Souza ; Salina, Ana Caroline Guerta ; Martins, Ronaldo ; Bonilha, Caio Santos ; Cunha, Larissa Dias ; Jamur, Maria Celia ; da Silva, Luis Lamberti Pinto ; Arruda, Eurico ; Zamboni, Dario Simoes ; Louzada-Junior, Paulo ; de Oliveira, Rene Donizeti Ribeiro ; Alves-Filho, Jose Carlos ; Cunha, Thiago Mattar ; Cunha, Fernando de Queiroz

• Tipo de documento: Artigo Científico
• Fonte: Journal of Infectious Diseases; v. 229, n. 5, p. 14-pg., 2023-12-18.

Resumo

Background Inflammation in the lungs and other vital organs in COVID-19 is characterized by the presence of neutrophils and a high concentration of neutrophil extracellular traps (NETs), which seems to mediate host tissue damage. However, it is not known whether NETs could have virucidal activity against SARS-CoV-2.Methods We investigated whether NETs could prevent SARS-CoV-2 replication in neutrophils and epithelial cells and what the consequence of NETs degradation would be in K18-humanized ACE2 transgenic mice infected with SARS-CoV-2.Results Here, by immunofluorescence microscopy, we observed that viral particles colocalize with NETs in neutrophils isolated from patients with COVID-19 or healthy individuals and infected in vitro. The inhibition of NETs production increased virus replication in neutrophils. In parallel, we observed that NETs inhibited virus abilities to infect and replicate in epithelial cells after 24 hours of infection. Degradation of NETs with DNase I prevented their virucidal effect in vitro. Using K18-humanized ACE2 transgenic mice, we observed a higher viral load in animals treated with DNase I. However, the virucidal effect of NETs was not dependent on neutrophil elastase or myeloperoxidase activity.Conclusions Our results provide evidence of the role of NETosis as a mechanism of SARS-CoV-2 viral capture and inhibition. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 20/05601-6 - Neutrophil extracelular traps (NETs): importância na patogênese e potencial alvo terapêutico na COVID-19
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Regular