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Front. Immunol. | doi: 10.3389/fimmu.2018.02174

Cell-mediated immune responses and immunopathogenesis of human Tick-borne encephalitis virus-infection

 Kim Blom1, 2*,  Angelica Cuapio1, 2,  John Tyler Sandberg1, 2,  Renata Varnaite1, 2,  Jakob Michaëlsson1, 2,  Niklas K. Björkström1, 2,  Johan K. Sandberg1, 2, Jonas Klingström1, 2, Lars Lindquist2, 3, Sara Gredmark Russ1, 2, 3 and  Hans-Gustaf Ljunggren1, 2*
  • 1Center for Infectious Medicine, Department of Medicine, Karolinska Institutet (KI), Sweden
  • 2Unit of Infectious Diseases, Department of Medicine, Karolinska Institutet (KI), Sweden
  • 3Department of Infectious Diseases, Karolinska University Hospital, Sweden

Tick-borne encephalitis virus (TBEV) is a flavivirus that belongs to the Flaviviridae family. TBEV is transmitted to humans primarily from infected ticks. The virus causes tick-borne encephalitis (TBE), an acute viral disease that affects the central nervous system (CNS). Infection can lead to acute neurological symptoms of significant severity due to meningitis or meningo(myelo)encephalitis. TBE can cause long-term suffering and has been recognized as an increasing public health problem. TBEV-affected areas currently include large parts of central and northern Europe as well as northern Asia. Mortality rates differ between infections with different TBEV strains. Infection with TBEV triggers a humoral as well as a cell-mediated immune response. In contrast to the well-characterized humoral antibody-mediated response, the cell-mediated immune responses elicited to natural TBEV-infection have been poorly characterized until recently. Here, we review recent progress in our understanding of the cell-mediated immune response to human TBEV-infection. A particular emphasis is devoted to studies of the response mediated by natural killer (NK) cells and CD8 T cells. The studies described include results revealing the temporal dynamics of the T cell- as well as NK cell-responses in relation to disease state and functional characterization of these cells. Additionally, we discuss specific immunopathological aspects of TBEV-infection in the CNS.

Keywords: cell-mediated immunity, Flavivirus, NK cells, T cells, Tick-borne encephalitis, Tick-borne encephalitis virus, Viral immunopathogenesis

Received: 27 Mar 2018; Accepted: 03 Sep 2018.

Edited by:

Alan C. Hsu, University of Newcastle, Australia

Reviewed by:

Alessandro Marcello, Inernational Centre for Genetic Engineering and Biotechnology, Italy
Manuela Zlamy, Innsbruck Medical University, Austria  

Copyright: © 2018 Blom, Cuapio, Sandberg, Varnaite, Michaëlsson, Björkström, Sandberg, Klingström, Lindquist, Gredmark Russ and Ljunggren. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
PhD. Kim Blom, Karolinska Institutet (KI), Center for Infectious Medicine, Department of Medicine, Solna, 14186, Sweden, kim.blom@ki.se
Prof. Hans-Gustaf Ljunggren, Karolinska Institutet (KI), Center for Infectious Medicine, Department of Medicine, Solna, 14186, Sweden, hans-gustaf.ljunggren@ki.se