Inflammatory Immune Responses in the Pathogenesis of Tick-Borne Encephalitis.

Clinical manifestations of tick-borne encephalitis (TBE) are thought to result from the host immune responses to infection, but knowledge of such responses is incomplete. We performed a detailed clinical evaluation and characterization of innate and adaptive inflammatory immune responses in matched serum and cerebrospinal fluid (CSF) samples from 81 adult patients with TBE. Immune responses were then correlated with laboratory and clinical findings. The inflammatory immune responses were generally site-specific. Cytokines and chemokines associated with innate and Th1 adaptive immune responses were significantly higher in CSF, while mediators associated with Th17 and B-cell responses were generally higher in serum. Furthermore, mediators associated with innate and Th1 adaptive immune responses were positively associated with disease severity, whereas Th17 and B cell immune responses were not. During the meningoencephalitic phase of TBE, innate and Th1 adaptive inflammatory mediators were highly concentrated in CSF, the site of the disease. The consequence of this robust immune response was more severe acute illness. In contrast, inflammatory mediators associated with B cell and particularly Th17 responses were concentrated in serum. These findings provide new insights into the immunopathogenesis of TBE and implicate innate and Th1 adaptive responses in severity and clinical presentation of acute illness.

Déclaration de conflit d'intérêts

Drs. Petra Bogovič, Lara Lusa, Miša Korva, Miša Pavletič, Katarina Resman Rus, Stanka Lotrič-Furlan, and Tatjana Avšič-Županc declare no conflict of interest. Dr. Klemen Strle served on the scientific advisory board for Roche for development of Lyme disease serological diagnostics received support by grant from MGH-ECOR. Dr. Franc Strle served on the scientific advisory board for Roche on Lyme disease serological diagnostics, received research support from the Slovenian Research Agency [grant number P3-0296], and is an unpaid member of the steering committee of the ESCMID Study Group on Lyme Borreliosis/ESGBOR. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.