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


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.

SUBMITTER: Coutinho-da-Silva MS 

PROVIDER: S-EPMC9193801 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

Coutinho-da-Silva Mikelly Santos MS   Sucupira Pedro Henrique Ferreira PHF   Bicalho Kelly Alves KA   Campi-Azevedo Ana Carolina AC   Brito-de-Sousa Joaquim Pedro JP   Peruhype-Magalhães Vanessa V   Rios Maria M   Teixeira-Carvalho Andréa A   Coelho-Dos-Reis Jordana Grazziela Alves JGA   Antonelli Lis Ribeiro do Valle LRDV   de Rezende Vitor Bortolo VB   de Melo Fernanda Ludolf Ribeiro FLR   Garcia Cristiana Couto CC   Silva-Andrade Jesuanne Carla JC   da Costa-Rocha Ismael Artur IA   Bastos Michele de Souza MS   da Rocha Lucia Alves LA   Silva Valderjane Aprigio VA   Ferreira Ewerton da Silva EDS   Marinho Eveny Perlize Melo EPM   Costa Allyson Guimarães AG   Gomes Matheus de Souza MS   Amaral Laurence Rodrigues LR   Furtado Erilene Cristina da Silva ECDS   da Silva Eliana Vieira Pinto EVP   Ramos Bruna Alves BA   Dos Santos Éder Barros ÉB   Freitas Maria Nazaré Oliveira MNO   Vasconcelos Pedro Fernando da Costa PFDC   Martins-Filho Olindo Assis OA   Araújo Márcio Sobreira Silva MSS   Ferreira Milene Silveira MS   Martins Livia Carício LC  

Frontiers in immunology 20220531


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,  ...[more]

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