Early Immune Hypoactivation and Persistent Innate Reprogramming Characterize Chronic Chikungunya Disease

Area of Science:

• Immunology
• Virology
• Pathogenesis

Background:

• Chikungunya virus (CHIKV) infection causes acute illness and can lead to chronic disease with persistent symptoms.
• The immunological basis for the transition from acute to chronic chikungunya disease is not well understood.

Purpose of the Study:

• To investigate the longitudinal immune profiles of patients with CHIKV infection stratified by clinical outcome.
• To identify immunological mechanisms underlying the development of chronic chikungunya disease.

Main Methods:

• Longitudinal immune profiling of CHIKV-infected patients.
• Single-cell RNA sequencing of peripheral blood mononuclear cells.
• Multiplex plasma cytokine analysis and flow cytometry.

Main Results:

• Patients developing chronic symptoms showed early innate immune hypoactivation and diminished adaptive immune activation during acute infection.
• Chronic progressors exhibited impaired monocyte-centered immune coordination and persistent innate immune remodeling six months post-infection.
• Divergent immune recovery trajectories were observed, particularly in non-classical monocytes and plasmacytoid dendritic cells.

Conclusions:

• Chronic chikungunya disease is associated with early innate immune hypoactivation followed by persistent innate immune remodeling.
• These findings offer insights into immune mechanisms contributing to post-viral chronic inflammatory syndromes.