AUTHOR=Coutinho-da-Silva Mikelly Santos , Sucupira Pedro Henrique Ferreira , Bicalho Kelly Alves , Campi-Azevedo Ana Carolina , Brito-de-Sousa Joaquim Pedro , Peruhype-Magalhães Vanessa , Rios Maria , Teixeira-Carvalho Andréa , Coelho-dos-Reis Jordana Grazziela Alves , Antonelli Lis Ribeiro do Valle , Rezende Vitor Bortolo de , Melo Fernanda Ludolf Ribeiro de , Garcia Cristiana Couto , Silva-Andrade Jesuanne Carla , Costa-Rocha Ismael Artur da , 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 Nazaré Oliveira , Vasconcelos Pedro Fernando da Costa , Martins-Filho Olindo Assis , Araújo Márcio Sobreira Silva , Ferreira Milene Silveira , Martins Livia Carício TITLE=Serum Soluble Mediator Profiles and Networks During Acute Infection With Distinct DENV Serotypes JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.892990 DOI=10.3389/fimmu.2022.892990 ISSN=1664-3224 ABSTRACT=

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.