Innate and adaptive immunity in wild rodents spontaneously and experimentally infected with the tick-borne encephalitis virus

Two dominant species of wild small rodents trapped in Novosibirsk region, South-Western Siberia, Russia differed in their susceptibility to the tick-borne encephalitis virus (TBEV) infection. TBEV RNA average detection rate for Northern red-backed vole Myodes rutilus (Pallas, 1779) (82.2 +/- 5.8% blood samples and 63.1 +/- 2.7% organ samples) significantly exceeded the corresponding values for the striped field mouse Apodemus agrarius (Pallas, 1771) (47.0 +/- 8.7% blood and 24.5 +/- 2.8% organ samples) (p < 0.001). Innate immunity may be one of possible reasons of the differences. Thl cytokine gene expression distinguished between M. rutilus (12.5 +/- 8.5%) and A. agrarius (66.6 +/- 11.4%), whereas Th2 cytokine frequencies were statistically similar (81.8 +/- 12.2% and 100.0%, respectively). Polarization indexes (PI) of the innate immunity calculated as ratio of Th2 to Thl cytokine RNA detection rates for both M. rutilus (6.5) and A. agrarius (1.5) suggested Th2 mainly humoral immune response against persistent TBEV in natural mammalian hosts. Therefore, the TBEV-induced antibodies were analyzed by ELISA and hemagglutination inhibition (HI) tests. The TBEV-specific antibodies were detected in 74.8 +/- 4.3% sera of M. rutilus and 67.3 +/- 6.8% of A. agrarius. Among them HI antibodies were found in 4.8 +/- 2.1% of the same analyzed sera of M. rutilus and in 6.0 +/- 3.4% blood samples of A. agrarius only. To model the TBEV persistence both M. rutilus and A. agrarius were infected with the suspensions of the TBEVinfected ticks with further observations during 4 subsequent months. Detection rate of the TBEV RNA and antigen E remained high during the whole period, however, pathogenic for laboratory suckling mice virus was isolated up to 8 days postinfection. At late stages of the persistent infection (1-4 months) the TBEV RNA detection rate in northern red-backed voles remained high 70.6 +/- 7.9% whereas in striped field mice significantly declined to 26.7 +/- 9.2% (p < .001). Comparative analysis of the innate immunity of the wild rodents in 2 months postinfection showed similar frequencies of Th2 cytokine gene expression for M. rutilus (77.8 +/- 10.1%) and A. agrarius (71.4 +/- 12.5%) (p > .05) but Thl cytokine mRNA detection rates were different (44.4 +/- 12.5% and 85.7 +/- 9.7%, respectively) (p < .05). In 2 months PI decreased from 6.5 until 1.75 for M. rutilus and from 1.5 until 0.83 for A. agrarius. Nevertheless, Th2 mainly humoral immune response was confirmed by direct detection of the TBEV-specific antibodies. HI and neutralizing antibodies were revealed in blood sera of the small rodents of both studied species in 30 days postinfection and remained at detectable levels during 4 months of observations. Accordingly, Th2 polarized innate immunity of small rodents might facilitate the TBEV intracellular persistence in the presence of HI and neutralization antibodies.