Page 391 - Avian Virology: Current Research and Future Trends

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to chickens (Röll et al., 2017). Suppressor of cytokine signalling CD57 (also known as HNK1) and CD5 and CD6 (reviewed in
proteins (SOCS1 and SOCS3) are up-regulated within hours Straub et al., 2013b), but their function is currently unknown.
and inhibit JAK/STAT signalling. USP18 maintains long term NK cells in mammals can express Fc receptors that bind to the Fc
desensitization by either removing ISG15 conjugated proteins or portion of immunoglobulins, allowing antibody-dependent cell-
binding intracellularly to IFNAR2. mediated cytotoxicity (ADCC) of antibody-coated target cells;
such activity has been described in chickens (Mándi et al., 1984).
Natural Killer cells In a virus infected cell, the activating signals dominate over
Natural Killer (NK) cells are effector lymphocytes of the innate inhibitory signals, leading to a direct attack of the infected cells
immune system that are known for their ability to kill virus- which is mediated by the secretion of cytolytic granules, contain-
infected cells. Their crucial role during the early phases of a virus ing perforin and granzymes which are pore forming proteins and
infection consists of two components. Primarily, they provide a serine proteases, respectively. A second pathway leading to NK
first line of defence against invading pathogens. Initially NK cells cell induced cell death is through the ligation of death domain
were thought to kill any cell that lacked MHC class I molecules receptors such as Fas and FasL. Although the NK cells themselves
(the so-called ‘missing self-hypothesis’), but it is now appreciated are difficult to define due to a limited number of monoclonal
that NK cells express a wide range of inhibitory and activating antibodies available for detection (Göbel et al., 2001; Jansen et
receptors, and that the balance between these signals determines al., 2010), NK cell activity during virus infections in the chicken
NK-cell activation (reviewed in Lanier, 2008). In general, the has been demonstrated for many viruses. NK cells have a key role
activating receptors have a short cytoplasmic tail with no sig- in containment of herpes viruses; they also play a role during
nalling motifs. Instead, signal transduction is mediated through the early cytolytic phase of MDV infection and MDV resistant
adaptor proteins such as CD3ζ and FcεRIγ with immunoreceptor and vaccinated birds have a greater NK cell activity than suscep-
tyrosine-based activation motifs (ITAMs) that associate with a tible unvaccinated birds (Sharma 1981; Heller and Schat, 1987;
charged transmembrane residue. In contrast, inhibitory recep- Garcia-Camacho et al., 2003; Sarson et al., 2008). Based on
tors lack the charged transmembrane residue, but have a long degranulation of NK cells, rapid activation at the site of infection,
cytoplasmic tail that contains immunoreceptor tyrosine-based the respiratory tract, has been demonstrated for IBV (Vervelde
inhibition motifs (ITIMs). et al., 2013a) and similar to mammals for IAV (Gazit et al., 2006;
In mammals two dominant receptor families have been Jansen et al., 2013). Enhanced activation of lung NK cells after
described, the killer cell immunoglobulin-like receptors (KIR, infection with LPAI virus was reported but infection with HPAI
CD158), a family of Ig domain containing transmembrane recep- virus resulted in decreased activation of lung NK cells, indicating
tors located in the leucocyte receptor complex (LRC), and the that decreased NK cell activation may be one of the mechanisms
Ly49 family that resemble type II transmembrane C-type lectin contributing to the pathogenicity of H5N1 HPAI viruses in
receptors located in the natural killer gene complex (NKC). In chickens (Jansen et al., 2013). The role of NK cells during IBDV
mammals, depending on the species one of the families has infections is not clearly defined, with a down-regulation of NK
expanded (Parham, 2008; Natarajan et al., 2002), but many lysin and functional impairment of NK cells described by two
additional receptors are found throughout the genome. The studies (Kumar et al., 1998; Rauf et al., 2011b) and no adverse
chicken LRC has been mapped to a small microchromosome and effect of IBDV infection on the NK cell activity reported by
contains a single multigene receptor family designated chicken Ig- another (Sharma and Lee, 1983).
like receptors (CHIRs). The annotation proves to be difficult due NK cell function extends far beyond killing of virus infected
to many highly homologous CHIR genes and pseudogenes and cells. Resting NK cells express receptors for numerous cytokines
therefore conclusions regarding the number and polymorphism that are produced by activated macrophages and can be rapidly
of the chicken LRC cannot be drawn (Laun et al., 2006; Lochner activated in response to stimulation by these cytokines. In turn
et al., 2010). The diversity seems to be higher than KIR and Ly49 the NK cells produce immunoregulatory cytokines including
(Viertlboeck et al., 2010), but based on amino acid identity, posi- IFNγ and tumour necrosis factor-α (TNFα), both enhancing
tion and nature of the basic transmembrane residue, associated NK cell cytotoxicity, IL-10 and IL-13 (Cooper et al., 2004).
adaptor molecule and genomic structure they are expected to rep- Moreover, NK cells interact with dendritic cells (DCs) leading
resent functional homologues of the receptor families encoded to DC maturation or apoptosis (Moretta, 2002; Cooper et al.,
by the LRC (Viertlboeck and Göbel, 2011). Most of the diverse 2004; Thomas and Yang, 2016; reviewed by Waggoner et al.,
C-type lectin receptors are represented in the chicken (reviewed 2016). In turn, DC-derived IL-12 drives the induction of IFNγ
in Straub et al., 2013b), but homologues of Ly49 are currently producing NK cells and IL-18 produced by DCs can further
only found in the genome of fowlpox virus (FPV). Interestingly, induce the expression of IL-12 receptor on NK cells (Walzer
one of the FPV-encoded C-type lectins is expressed on the sur- et al., 2005). Plasmacytoid DCs (pDCs) are producers of large
face of virus infected cells and may enable the virus to prevent NK amounts of IFNα/β which induce NK cell cytotoxicity (Biron
mediated lysis (Wilcock et al., 1999; Afonso et al., 2000). Other et al., 1999). This cross talk is evident in viral infections of
potential NK cell receptors in the chicken have been identified in humans such as HIV (reviewed by Altfeld et al., 2011) and
the chicken genome, including signalling lymphocytic activation hepatitis C virus (Jinushi et al., 2004), but yet to be published
molecule (SLAM) family members (Straub et al., 2013a), CD56, in avian viral infections.