Serum Soluble Mediator Profiles and Networks During Acute Infection With Distinct DENV Serotypes

• Autor(a) principal: Mikelly Santos Coutinho-da-Silva
• Data de Publicação: 2022
• Outros Autores: Lis Ribeiro do Valle Antonelli, Vitor Bortolo de Rezende, Fernanda Ludolf Ribeiro de Melo, Cristiana Couto Garcia, Jesuanne Carla Silva-Andrade, Ismael Artur da Costa-Rocha, Michele de Souza Bastos, Lucia Alves da Rocha, Valderjane Aprigio Silva, Ewerton da Silva Ferreira, Pedro Henrique Ferreira Sucupira, Eveny Perlize Melo Marinho, Allyson Guimarães Costa, Matheus de Souza Gomes, Laurence Rodrigues Amaral, Erilene Cristina da Silva Furtado, Eliana Vieira Pinto da Silva, Bruna Alves Ramos, Éder Barros Dos Santos, Maria Nazaré Oliveira Freitas, Pedro Fernando da Costa Vasconcelos, Kelly Alves Bicalho, Olindo Assis Martins-Filho, Márcio Sobreira Silva Araújo, Milene Silveira Ferreira, Livia Carício Martins, Ana Carolina Campi-Azevedo, Joaquim Pedro Brito-de-Sousa, Vanessa Peruhype-Magalhães, Maria Rios, Andrea Teixeira-Carvalho, Jordana Grazziela Alves Coelho Dos Reis
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFMG
• Texto Completo: https://doi.org/10.3389/fimmu.2022.892990; http://hdl.handle.net/1843/61471
• topic: Dengue infection; Dengue virus; Immune response; DENV serotypes; Chemokines; Cytokines; Citocinas; Quimiocinas; Sorogrupo; Imunidade; Dengue

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-γ, 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.