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Monocyte Dynamics in Chikungunya Fever: Sustained Activation and Vascular-Coagulation Pathway Involvement
Caroline Fernandes Dos Santos1, Priscila Conrado Guerra Nunes1, Victor Edgar Fiestas-Solorzano1
1Laboratório das Interações Vírus Hospedeiros, Instituto Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil.
Insights
Chikungunya virus infection activates specific monocyte subsets, increasing TLR4 and TLR7 expression. This immune activation, marked by elevated soluble CD163, suggests potential therapeutic targets for Chikungunya fever.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Chikungunya fever (CF), caused by Chikungunya virus (CHIKV), presents with debilitating joint pain.
- Monocytes are crucial for immune response and viral replication during CHIKV infection.
Purpose of the Study:
- To evaluate the clinical and immunological profiles of patients with laboratory-confirmed Chikungunya fever.
- To investigate the role of monocyte subsets and associated immune markers in CHIKV infection.
Main Methods:
- Analysis of clinical symptoms and laboratory-confirmed CHIKV-infected patients.
- Flow cytometry to assess Toll-like receptor (TLR) expression on monocyte subsets (CD14+CD16+, CD14+CD16++).
- Measurement of soluble CD163 (sCD163), Tissue Factor (TF), Tissue Factor Pathway Inhibitor (TFPI), Epidermal Growth Factor (EGF), and Vascular Endothelial Growth Factor (VEGF) levels.
Main Results:
- Increased TLR4 expression in non-classical monocytes (CD14+CD16++) and enriched TLR7+ intermediate (CD14+CD16+) and non-classical monocytes during acute and chronic phases.
- Elevated sCD163 levels indicate sustained monocyte/macrophage activation.
- Increased coagulation mediators (TF, TFPI) observed, despite rare hemorrhagic events.
- Patients with arthritis showed higher TLR7+ intermediate monocytes and EGF; those with edema had increased VEGF.
Conclusions:
- CHIKV infection induces differential activation of CD16+ monocyte subsets.
- Elevated TLR expression and sCD163 suggest prolonged immune pathway activation and serve as markers of monocyte/macrophage activation in CHIKV infection.
- Specific monocyte profiles correlate with clinical manifestations like arthritis and edema.
Abstract:
Chikungunya fever (CF), caused by the Chikungunya virus (CHIKV), is characterized by disabling symptoms such as joint pain that can last for months. Monocytes play a central role in immune modulation and viral replication during infection. This study evaluated the clinical and immunological profiles of patients with laboratory-confirmed CF. Fever and joint pain were the most frequently reported symptoms, whereas edema was more common in women. CHIKV-infect individuals exhibited increased TLR4 expression in non-classical monocytes (CD14+CD16++). Additionally, intermediate (CD14+CD16+) and non-classical (CD14+CD16++) monocytes expressing TLR7 were enriched during the acute phase and in some chronic patients, thereby suggest prolonged TLR7 pathway activation. Levels of soluble CD163 (sCD163)-a marker of monocyte/macrophage activation-were elevated as well, indicating sustained immune activation. Coagulation-related mediators-including Tissue factor (TF) and Tissue factor pathway inhibitor (TFPI)-also increased, despite the rarity of hemorrhagic events or thrombocytopenia. Patients with arthritis demonstrated higher frequencies of TLR7+ intermediate monocytes and elevated Epidermal growth factor (EGF) levels, whereas those with edema exhibit increased Vascular endothelial growth factor (VEGF) levels. Overall, these findings highlighted the differential activation of CD16+ monocytes and suggested that sCD163 is a marker of monocyte/macrophage activation during CHIKV infection.
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