Mice with different susceptibility to tick-borne encephalitis virus infection show selective neutralizing antibody response and inflammatory reaction in the central nervous system

0397212 - BC 2014 RIV GB eng J - Článek v odborném periodiku
Palus, Martin - Vojtíšková, Jarmila - Salát, Jiří - Kopecký, Jan - Grubhoffer, Libor - Lipoldová, Marie - Demant, P. - Růžek, Daniel
Mice with different susceptibility to tick-borne encephalitis virus infection show selective neutralizing antibody response and inflammatory reaction in the central nervous system.
Journal of Neuroinflammation. Roč. 10, JUN 2013 (2013), s. 77. E-ISSN 1742-2094
Grant CEP: GA ČR GAP502/11/2116
Grant ostatní: GA MŠk(CZ) ED0006/01/01
Institucionální podpora: RVO:60077344 ; RVO:68378050
Klíčová slova: Tick-borne encephalitis * Flavivirus encephalitis * Neuroinflammation * Antibody production
Kód oboru RIV: EC - Imunologie; EB - Genetika a molekulární biologie (UMG-J)
Impakt faktor: 4.902, rok: 2013

Methods: TBE virus growth, neutralizing antibody response, key cytokine and chemokine mRNA production and changes in mRNA levels of cell surface markers of immunocompetent cells in brain were measured in mice with different susceptibilities to TBE virus infection. Results: An animal model of TBE based on BALB/c-c-STS/A (CcS/Dem) recombinant congenic mouse strains showing different severities of the infection in relation to the host genetic background was developed. After subcutaneous inoculation of TBE virus, BALB/c mice showed medium susceptibility to the infection, STS mice were resistant, and CcS-11 mice were highly susceptible. The resistant STS mice showed lower and delayed viremia, lower virus production in the brain and low cytokine/chemokine mRNA production, but had a strong neutralizing antibody response. The most sensitive strain (CcS-11) failed in production of neutralizing antibodies, but exhibited strong cytokine/chemokine mRNA production in the brain. After intracerebral inoculation, all mouse strains were sensitive to the infection and had similar virus production in the brain, but STS mice survived significantly longer than CcS-11 mice. These two strains also differed in the expression of key cytokines/chemokines, particularly interferon gamma-induced protein 10 (IP-10/CXCL10) and monocyte chemotactic protein-1 (MCP-1/CCL2) in the brain. Conclusions: Our data indicate that the genetic control is an important factor influencing the clinical course of TBE. High neutralizing antibody response might be crucial for preventing host fatality, but high expression of various cytokines/chemokines during TBE can mediate immunopathology and be associated with more severe course of the infection and increased fatality.
Trvalý link: http://hdl.handle.net/11104/0224863