Serum soluble mediator profiles and networks during acute infection with distinct DENV serotypes

• Autor(a) principal: Silva, Mikelly Santos Coutinho da
• Data de Publicação: 2022
• Outros Autores: Sucupira, Pedro Henrique Ferreira, Bicalho, Kelly Alves, Campi-Azevedo, Ana Carolina, Sousa, Joaquim Pedro Brito de, Magalhães, Vanessa Peruhype, Rios, Maria, Carvalho, Andréa Teixeira, Reis, Jordana Grazziela Alves Coelho dos, Antonelli, Lis Ribeiro do Valle, Rezende, Vitor Bortolo de, Melo, Fernanda Ludolf Ribeiro de, Garcia, Cristiana Couto, Andradre, Jesuanne Carla Silva, Rocha, Ismael Artur da Costa, Bastos, Michele de Souza, Rocha, Lucia Alves da, Silva, Valderjane Aprigio, Ferreira, Ewerton da Silva, Marinho, Eveny Perlize Melo, Costa, Allyson Guimarães, Gomes, Matheus de Souza, Amaral, Laurence Rodrigues, Furtado, Erilene Cristina da Silva, Silva, Eliana Vieira Pinto da, Ramos, Bruna Alves, Santos, Éder Barros dos, Freitas, Maria de Nazaré Oliveira, Vasconcelos, Pedro Fernando da Costa, Martins Filho, Olindo Assis, Araújo, Márcio Sobreira Silva, Ferreira, Milene Silveira, Martins, Lívia Caricio
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Digital do Instituto Evandro Chagas (Patuá)
• Texto Completo: https://patua.iec.gov.br/handle/iec/4567
• topic: Dengue / patologia; Biomarcadores; Quimiocinas / análise; Patogênese Homeopática

A panoramic analysis of chemokines, pro-inflammatory/regulatory cytokines, and growth factors was performed in serum samples from patients with acute DENV infection (n=317) by a high-throughput microbeads array. Most soluble mediators analyzed were increased in DENV patients regardless of the DENV serotype. The substantial increase (>= 10-fold) of CXCL10, IL-6, and IFN-gamma, and decreased levels of PDGF (<0.4-fold) was universally identified in all DENV serotypes. Of note, increased levels of CXCL8, CCL4, and IL-12 (>= 3-9-fold) were selectively observed in DENV2 as compared to DENV1 and DENV4. Heatmap and biomarker signatures further illustrated the massive release of soluble mediators observed in DENV patients, confirming the marked increase of several soluble mediators in DENV2. Integrative correlation matrices and networks showed that DENV infection exhibited higher connectivity among soluble mediators. Of note, DENV2 displayed a more complex network, with higher connectivity involving a higher number of soluble mediators. The timeline kinetics (Day 0-1, D2, D3, D4-6) analysis additionally demonstrated differences among DENV serotypes. While DENV1 triggers a progressive increase of soluble mediators towards D3 and with a decline at D4-6, DENV2 and DENV4 develop with a progressive increase towards D4-6 with an early plateau observed in DENV4. Overall, our results provided a comprehensive overview of the immune response elicited by DENV infection, revealing that infection with distinct DENV serotypes causes distinct profiles, rhythms, and dynamic network connectivity of soluble mediators. Altogether, these findings may provide novel insights to understand the pathogenesis of acute infection with distinct DENV serotypes.