Elevated NS1 serum levels reduce CD119 expression and CXCL-10 synthesis in patients with dengue hemorrhagic fever

Rev Soc Bras Med Trop. 2024 Jul 29:57:e00410. doi: 10.1590/0037-8682-0577-2023. eCollection 2024.

Abstract

Background: The intensity of dengue virus (DV) replication and circulating non-structural protein 1 (NS1) levels may promote changes in the human immune response and favor severe forms of infection. We investigated the correlations between NS1 with CXCL-8, CXCL-10, IFN-γ, and IL-12p40 serum levels, and IFN-γ receptor α chain (CD119) expression, and CXCL10 production by peripheral blood mononuclear cells (PBMCs) stimulated with recombinant IFN-γ in DV-infected patients with different clinical forms.

Methods: Dengue virus NS1, CXCL-8, CXCL-10, IFN-γ, and IL-12p40 serum levels were measured in 152 DV-infected patients with different clinical forms and 20 non-infected individuals (NI) using enzyme-linked immunosorbent assay (ELISA). In addition, we investigated the CXCL-10 production after in vitro IFN-γ stimulation of PBMCs from 48 DV-infected individuals (with different clinical forms of dengue fever) and 20 NI individuals using ELISA, and CD119 expression on CD14+ cells with flow cytometry.

Results: Patients with dengue hemorrhagic fever (DHF) had significantly higher NS1, CXCL-8, and CXCL-10 serum levels than those with classic dengue fever (DF). The response of PBMCs to IFN-γ stimulation was lower in patients with DHF than in those with DF or dengue with complications (DWC), with lower CD119 expression and reduced CXCL-10 synthesis. In addition, these alterations are associated with high NS1 serum levels.

Conclusions: Patients with DHF reported high NS1 levels, low CD119 expression, and low CXCL-10 synthesis in PBMCs, which may be associated with infection progression and severity.

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Chemokine CXCL10* / blood
  • Enzyme-Linked Immunosorbent Assay*
  • Female
  • Flow Cytometry
  • Humans
  • Interferon-gamma / blood
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Severe Dengue* / blood
  • Severe Dengue* / immunology
  • Viral Nonstructural Proteins*
  • Young Adult

Substances

  • Chemokine CXCL10
  • Viral Nonstructural Proteins
  • Interferon-gamma