The Role of Chemotactic Cytokines in Tick-Borne Encephalitis
Sambor Grygorczuk1, Piotr Czupryna1, Diana Martonik2
1Department of the Infectious Diseases and Neuroinfections, Medical University in Białystok, 15-089 Białystok, Poland.
Insights
In tick-borne encephalitis (TBE), specific cytokines like CXCL1 and IL-8 drive leukocyte infiltration into the central nervous system (CNS). These cytokine profiles correlate with disease severity but not genetic variations, highlighting complex immune responses in TBE.
Area of Science:
- Neuroimmunology
- Virology
- Molecular Biology
Background:
- Tick-borne encephalitis (TBE) involves central nervous system (CNS) inflammation due to leukocyte infiltration.
- Understanding the role of chemotactic cytokines is crucial for TBE pathogenesis and immune response.
Purpose of the Study:
- To investigate the relationship between cytokine concentrations, leukocyte infiltration (pleocytosis), and clinical severity in TBE patients.
- To explore the influence of cytokine gene polymorphisms on TBE immune responses.
Main Methods:
- Measured 25 cytokines in serum and cerebrospinal fluid (CSF) of 103 TBE patients.
- Correlated cytokine levels with CSF leukocyte counts and clinical severity.
- Analyzed ten cytokine/receptor gene polymorphisms using rtPCR.
Main Results:
- Strong chemotactic gradients towards CSF were identified for CXCL1, IL-8, CXCL10, CCL2, and others.
- Neutrophil counts correlated with CXCL1 and IL-8; lymphocyte counts correlated with IL-16, CCL19, CCL20, CCL4, CXCL12, and CXCL13.
- Milder TBE associated with CCL11, CCL19, CXCL10, CXCL13; severe TBE with CXCL1, CCL20. Gene polymorphisms affected cytokine levels and pleocytosis, not clinical severity.
Conclusions:
- Multiple chemotactic cytokines orchestrate leukocyte infiltration in TBE.
- The relationship between cytokine-driven pleocytosis and clinical presentation is complex and not always direct.
Abstract:
In tick-borne encephalitis (TBE), the central nervous system (CNS) is infiltrated by a mixed leukocyte population contributing both to the infection control and the immune-mediated pathology. To elucidate the roles of chemotactic cytokines in this process, we measured concentrations of 25 cytokines in serum and cerebrospinal fluid (CSF) simultaneously with total CSF leukocyte count (pleocytosis) and leukocyte subpopulation counts in 103 TBE patients. We created models describing the dependence of pleocytosis and clinical severity on cytokine concentrations. Ten polymorphisms in genes for cytokines or their receptors were studied with rtPCR in patients' DNA samples. The strongest chemotactic gradients towards CSF were created by CXCL1, IL-8, CXCL10, CCL2, CCL3, CCL4, CCL7, CCL8, CCL19 and CCL20. Neutrophil counts in CSF correlated with concentrations of CXCL1 and IL-8 and lymphocyte counts with IL-16, CCL19, CCL20, CCL4, CXCL12, and CXCL13. The milder disease is associated with CCL11, CCL19, CXCL10 and CXCL13,-while the more severe with CXCL1 and CCL20. The polymorphisms in the genes CCR2, CCL5, CXCR3 and CX3CR1 are associated with the cytokine concentrations and pleocytosis, but not with clinical severity. Multiple chemotactic cytokines contribute to pleocytosis in TBE, with no straightforward relationship between their effects on pleocytosis and the clinical presentation.
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