Page 168 - TBE_Book_V2_2019

Chapter 9: Immunology of TBEV infection

toms of different severity, ranging from TBE disease progression
meningitis to severe meningoencephalitis (as
1
reviewed in ). The first phase of TBE is Barriers and local transmission of
challenging to study in humans, as infected TBEV
individuals rarely seek medical attention.
Therefore, sampling from blood or tissues Skin is one of the first physical barriers of the
from humans to study TBE is mostly possible host that prevents the entry of pathogenic
during the second phase of disease. microorganisms. However, it is not purely a
Interestingly, upon the emergence of neuro- physical barrier, it is also equipped with many
logical symptoms, the virus can no longer be specialized immune cells, such as
detected in peripheral blood and cere- macrophages, mast cells, dendritic cell (DC)
2
brospinal fluid (CSF). Whether as of this time subsets, T cell subsets, and natural killer T cells
the virus persists in other locations in the body ready to respond to any threatening
(e.g. the brain parenchyma) has yet to be microorganism. TBEV is mainly transferred to
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investigated. humans through the bite of infected ticks.
The pathogenesis of TBE is also not completely Thus, the skin is the primary site of viral
understood. It may be attributed to either the transmission from the tick’s saliva to the host.
direct viral cytolytic effects or the immune cell Virus transmission from the tick is facilitated
-mediated tissue damage, or both. TBEV viral by ‘‘saliva-activated transmission” factors
proteins and immune cell infiltrates have been within the tick’s saliva which contains
detected in neuronal tissues from fatal TBE components that interfere with the immune
cases supporting both mechanisms of response, including factors that block and
3,4
pathogenesis – at least in such cases. modulate inflammation, haemostasis, innate
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and acquired immunity, and wound healing.
In this chapter of the book, we aim to Already within the first hour of feeding, a
summarize the current understanding of the stronger inflammatory micro-environment
immune system responses to TBEV infection with increased cell recruitment is created at
(Figure 1). First, we discuss the initial stages of
the TBEV-infected tick feeding site, as
TBE development including host barriers, viral compared to uninfected tick feeding sites.
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spread, mechanisms of TBEV entry into the
CNS and innate immune responses, most of After TBEV is transmitted, the cells residing in
which are delineated from in vitro or mouse the skin tissue are exposed to the virus. Tick-
models. We later review the adaptive immune feeding experiments in mice show that
system responses to TBEV infection, both dendritic cells (DCs), mononuclear phagocytes
humoral and cellular, from studies conducted and fibroblasts are the main cells to be
7,8
primarily on human peripheral blood and CSF infected by TBEV in the skin. Tick saliva
compartments. further modulates TBEV infection of DCs by
increasing their susceptibility to the virus and
Throughout this chapter, we also highlight the
decreasing their ability to release inflame-
observed correlations between human matory cytokines. Mononuclear phagocytes
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immune responses and clinical TBE disease and DCs are believed to be involved in viral
outcomes. dissemination of TBEV, as these cells can
migrate from the skin to the draining lymph
nodes.

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