Human dermal fibroblast-derived factors from sequential DENV-2 and ZIKV coinfection drive dendritic cell maturation and antiviral responses.

Bibliographic Details
Title: Human dermal fibroblast-derived factors from sequential DENV-2 and ZIKV coinfection drive dendritic cell maturation and antiviral responses.
Authors: Kaofai C; Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand; Division of Microbiology and Parasitology, School of Medical Sciences, University of Phayao, Phayao, Thailand., Limthongkul J; Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand., Boonsilp S; Department of Clinical Pathology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand., Ubol S; Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand. Electronic address: Sukathida.ubo@mahidol.ac.th., Jearanaiwitayakul T; Department of Clinical Pathology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand. Electronic address: Tuksin.jea@nmu.ac.th.
Source: Virology [Virology] 2026 Oct; Vol. 623, pp. 111000. Date of Electronic Publication: 2026 Jun 05.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Academic Press Country of Publication: United States NLM ID: 0110674 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0341 (Electronic) Linking ISSN: 00426822 NLM ISO Abbreviation: Virology Subsets: MEDLINE
Imprint Name(s): Original Publication: New York, Academic Press.
MeSH Terms: Dendritic Cells*/immunology , Dendritic Cells*/virology , Fibroblasts*/immunology , Fibroblasts*/virology , Fibroblasts*/metabolism , Dengue Virus*/immunology , Dengue Virus*/physiology , Zika Virus*/immunology , Zika Virus*/physiology , Coinfection*/virology , Coinfection*/immunology , Dengue*/immunology , Dengue*/virology , Zika Virus Infection*/immunology , Zika Virus Infection*/virology, Cytokines/immunology ; Cytokines/metabolism ; Skin/immunology ; Skin/cytology ; Skin/virology ; Dermis/cytology ; Dermis/immunology ; Humans ; Cells, Cultured
Abstract: Dengue virus (DENV) and Zika virus (ZIKV) are among the most prevalent mosquito-borne viruses worldwide. These viruses co-circulate in the same geographical regions and share the same mosquito vectors, enabling concurrent or sequential transmission to humans within a short period. During the early phase of arbovirus infection, skin-resident cells constitute the first line of defense following viral inoculation, yet the immunological events in the skin microenvironment during early DENV-ZIKV coinfection are not well understood. This study aimed to investigate the response of primary human dermal fibroblasts (HDFs) to DENV-ZIKV coinfection and to determine how these responses influence bystander immune cells within an in vitro. We demonstrated that sequential infection with DENV-2 followed by ZIKV significantly increased the expression of pro-inflammatory cytokines (IL-6, IL-8, IL-1β), leukocyte migration-associated chemokine (CXCL10), and antiviral mediators (IFN-β and IFN-λ) in HDFs. Primary monocyte-derived dendritic cells (moDCs) exposed to soluble mediators from sequentially coinfected HDFs exhibited greater activation marker expression compared with simultaneous coinfection or monoinfection conditions. Furthermore, these mediators conferred antiviral effects against both DENV-2 and ZIKV infection in treated moDCs. These findings highlight the important role of dermal fibroblasts in shaping adaptive immunity and limiting viral spread during DENV and ZIKV coinfection.
(Copyright © 2026 Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: Coinfection; Dendritic cells; Dengue virus; Human dermal fibroblasts; Skin immune response; Zika virus
Substance Nomenclature: 0 (Cytokines)
Entry Date(s): Date Created: 20260608 Date Completed: 20260723 Latest Revision: 20260723
Update Code: 20260724
DOI: 10.1016/j.virol.2026.111000
PMID: 42259182
Database: MEDLINE
Description
ISSN:1096-0341
DOI:10.1016/j.virol.2026.111000