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Chapter 4: Pathogenesis of TBE

type I IFNs, but they also play a critical role in Antigen-presenting cells
immunoregulation during the development of
adaptive immunity, thereby bridging innate Effective host defense against infection
and adaptive immune responses. Their requires innate and adaptive immune
important role in the host defense against responses working together to mediate
viruses is supported by the finding that clearance of invading pathogens. Dendritic
humans with complete or partial impairment cells (DCs) bridge these 2 arms of immunity. In
of NK cell numbers and functions have peripheral tissues, immature DCs recognize
increased susceptibilities to viral infections, RNA virus infection, migrate to local lymphoid
including HSV, varicella zoster virus, CMV, and tissues, and undergo a process of maturation
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human papilloma virus. that involves cytokine production and antigen
presentation to activate naïve T cells and
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NK cells have been studied in various flavivirus shape adaptive immunity. Many flaviviruses
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infections including DENV, WNV, JEV and including DENV, WNV, and JEV, infect DCs
yellow fever virus (YFV). NK cells have been resulting in impaired DC maturation and T cell
suggested to affect disease severity and priming/proliferation and promoting viral
outcome, as well as to contribute to viral pathogenesis. DCs also represent early targets
control, even though the underlying of TBEV infection following the bite from an
mechanisms remain unknown. 63-65 The role of infected tick, providing the virus with
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NK cells in immunopathology of TBEV opportunities to manipulate DC functions as a
infection is largely unknown. Langat or TBEV means of evading host immunity. LGTV
infection in mice leads to a temporary infection impairs DC maturation by suppres-
activation of NK cells during the early phase of sion of costimulatory molecules and inhibition
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infection, followed by suppression, which in of IL-12 production. This immature DC
later phases of infection was not associated phenotype was associated with an impaired
with increased viral replication in splenocytes. functional capacity to induce T cell pro-
Ex vivo infection of whole-blood cells showed liferation. However, how this is involved in
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activation of NK cells only with low pathogenic viral pathogenesis is unknown.
TBEV strains while highly pathogenic TBEV
inhibits NK cell activation. Decreased
expression of perforin and granzyme B was
detected in activated CD56dim NK cells of Adaptive Immune response to
TBEV-infected patients during hospitalization, TBEV
indicating that cytotoxic granules were
released early in NK cell activation and Humoral immunity
symptom onset, thereby possibly contributing
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to pathogenesis of infection. Given these Humoral immunity is an important component
ostensibly conflicting results, more investi- of the immune response. As with other
gation is needed to determine the functional flaviviruses, a functional humoral immune
role of NK cells in limiting viral replication and response is critically important in controlling
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in the pathology associated with TBEV infections. Passive transfer of monoclonal or
infection in different hosts. polyclonal TBEV-specific antibodies protects
mice in vivo and protection correlates with in
vitro neutralization. 74-77 No infectious virus
could be detected in the blood or brain of
passively protected mice subsequent to TBEV

challenge. However, antibodies protect not

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