The expression of the chemokine receptor CCR5 in tick-borne encephalitis
Sambor Grygorczuk1, Joanna Osada2, Miłosz Parczewski3
1Department of the Infectious Diseases and Neuroinfections, Medical University of Białystok, ul. Żurawia 14, 15-540, Białystok, Poland. grygorczuk.sambor@neostrada.pl.
Background:
Chemokine receptor 5 (CCR5) is hypothesized to drive the lymphocyte migration to central nervous system in flavivirus encephalitis, and the non-functional CCR5Δ32 genetic variant was identified as a risk factor of a West Nile virus infection and of tick-borne encephalitis (TBE). We have attempted to investigate how CCR5 expression corresponds to the clinical course and severity of TBE.
Methods:
We have repeatedly studied CCR5 expression in 76 patients during encephalitic and convalescent TBE phase, analyzing its association with clinical features, cerebrospinal fluid (csf) pleocytosis, and concentrations of CCR5 ligands (chemokines CCL3, CCL4, and CCL5) and CCR5 genotype. Fifteen patients with neuroborreliosis, 7 with aseptic meningitis, 17 in whom meningitis/encephalitis had been excluded, and 18 healthy blood donors were studied as controls. Expression of CCR5 was measured cytometrically in blood and csf-activated Th lymphocytes (CD3+CD4+CD45RO+). Concentrations of chemokines in serum and csf were measured immunoenzymatically, and CCR5Δ32 was detected with sequence-specific primers. Data were analyzed with non-parametric tests, and p < 0.05 was considered significant.
Results:
The blood expression of CCR5 did neither differ between the groups nor change in the course of TBE. The CCR5 expression in the inflammatory csf was several-fold increased in comparison with blood but lower in TBE than in neuroborreliosis. The csf concentration of CCL5 was increased in TBE, the highest in the most severe presentation (meningoencephalomyelitis) and correlated with pleocytosis. The CCR5Δ32/wt genotype present in 7 TBE patients was associated with a decreased CCR5 expression, but enrichment of csf Th population in CCR5-positive cells and the intrathecal inflammatory response were preserved, without a compensatory increase of CCL5 expression.
Conclusions:
We infer CCR5 and CCL5 participate in the response to TBE virus, as well as to other neurotropic pathogens. The intrathecal response to TBE is not hampered in the bearers of a single copy of CCR5Δ32 allele, suggesting that the association of CCR5Δ32 with TBE may be mediated in the periphery at the earlier stage of the infection. Otherwise, a variability of the CCR5 expression in the peripheral blood lymphocytes seems not to be associated with a variable susceptibility to TBE.
