Innate Immune Cytokine Profiling and Biomarker Identification for Outcome in Dengue Patients

Area of Science:

• Immunology
• Infectious Diseases
• Biomarker Discovery

Background:

• Severe dengue requires early biomarkers for effective patient management and cost control.
• Innate immune cells and their secreted cytokines are critical in dengue pathogenesis, potentially leading to a "cytokine storm" in severe cases.
• This study investigated the early innate immune cytokine profiles in dengue patients during the acute phase.

Purpose of the Study:

• To identify early innate immune biomarkers capable of predicting progression to severe dengue.
• To understand the role of innate immune responses in dengue severity.

Main Methods:

• Prospective, blinded study including dengue patients, febrile controls, and healthy controls.
• Utilized intracellular cytokine staining and flow cytometry to analyze innate immune cells and cytokine secretion.
• Investigated cytokine profiles (e.g., TNF-α, IFN-γ, IL-6) from various innate immune cell subsets.

Main Results:

• Dengue infection enhanced cytokine secretion (TNF-α, IFN-γ) from innate immune cells, including NKT cells, monocytes, and granulocytes.
• Higher proportions of TNF-α secreting granulocytes and monocytes at admission correlated with milder dengue.
• Dengue NS1 antigenemia (viral load surrogate) correlated with cytokine-secreting innate immune cells and milder recovery.
• Compromised early activation and downregulation of innate responses were observed in patients with secondary dengue or severe outcomes.

Conclusions:

• Faulty or delayed innate immune activation/downregulation kinetics drive dengue severity.
• Interferon-gamma (IFN-γ)+CD56+CD3+ NKT cells and Interleukin-6 (IL-6)+ granulocytes at admission are novel early biomarkers predicting severe dengue risk (AUC=0.85-0.9).
• Coordinated early activation of the innate immune system contributes to infection resolution and recovery.