DENV-Specific IL-10-Producing Regulatory T Cells Are Associated With Mild Clinical Outcomes in Dengue

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Dengue infection presents with varying severity, from mild to life-threatening. Severe dengue is linked to uncontrolled immune responses.
• Regulatory T cells (Tregs) are vital for immune homeostasis but their role in dengue pathogenesis remains understudied.

Purpose of the Study:

• To investigate the phenotype and function of Tregs in different clinical forms of dengue infection.
• To understand the association between Treg profiles and dengue disease severity.

Main Methods:

• Collected plasma and peripheral blood mononuclear cells (PBMCs) from healthy donors and dengue patients.
• Cultured PBMCs with DENV1 viral protein peptides (ENV and NS3).
• Analyzed Treg frequencies, cytokine profiles (IL-10, IFNγ, TNF), and expression of markers like GITR, CD200, and PD1.

Main Results:

• Dengue with warning signs (WS+) patients had higher IL-10 during the febrile phase compared to mild dengue.
• Mild dengue cases showed balanced pro-inflammatory and regulatory cytokines, and higher frequencies of GITR+ and CD200+ Tregs.
• WS+ patients exhibited increased PD1+ Tregs, indicative of dysfunction, and lacked DENV-specific GITR+ Tregs producing IL-10.

Conclusions:

• Altered Treg phenotypes are observed in WS+ dengue patients.
• The presence of IL-10-producing DENV-specific GITR+ Tregs and CD200+ Tregs is associated with mild dengue presentation.
• These Treg-mediated regulatory mechanisms are crucial in limiting dengue immunopathology.