AUTHOR=Moragas Leandro Junqueira , Alves Felipe de Andrade Vieira , Oliveira Lucca de Lima Siqueira , Salomão Natália Gedeão , Azevedo Caio Gonçalves , da Silva Jemima Fuentes Ribeiro , Basílio-de-Oliveira Carlos Alberto , Basílio-de-Oliveira Rodrigo , Mohana-Borges Ronaldo , de Carvalho Jorge José , Rosman Fernando Colonna , Paes Marciano Viana , Rabelo Kíssila TITLE=Liver immunopathogenesis in fatal cases of dengue in children: detection of viral antigen, cytokine profile and inflammatory mediators JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1215730 DOI=10.3389/fimmu.2023.1215730 ISSN=1664-3224 ABSTRACT=Introduction

Dengue virus (DENV), the etiologic agent of dengue fever illness, represents a global public health concern, mainly in tropical and subtropical areas across the globe. It is well known that this acute viral disease can progress to severe hemorrhagic stages in some individuals, however, the immunopathogenic basis of the development of more severe forms by these patients is yet to be fully understood.

Objective

In this context, we investigated and characterized the histopathological features as well as the cytokine profile and cell subpopulations present in liver tissues from three fatal cases of DENV in children.

Methods

Hematoxylin and Eosin, Periodic Acid Schiff and Picro Sirius Red staining were utilized for the histopathological analysis. Immunohistochemistry assay was performed to characterize the inflammatory response and cell expression patterns.

Results

Vascular dysfunctions such as hemorrhage, vascular congestion and edema associated with a mononuclear infiltrate were observedin all three cases. Liver tissues exhibited increased presence of CD68+ and TCD8+ cells as well as high expression of MMP-9, TNF-a, RANTES, VEGFR-2 mediators. Viral replication was confirmed by the detection of NS3 protein.

Conclusion

Taken together, these results evidenced key factors that may be involved in the development of severe alterations in liver tissues of children in response to DENV infection.