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different strains of infectious bursal disease virus (IBDV) (Rauf et The concept of the host’s innate immune system recognizing
al., 2011a) whereas both high and low pathogenicity avian influ- a diverse set of PAMPS through innate germline encoded recep-
enza (HPAI and LPAI) viruses up-regulate TLR3, although the tors to generate effective immune responses is oversimplified.
kinetics of the response differs in ducks compared with chickens This principle ignores the contextual information that will allow
(Karpala et al., 2008a; Cornelissen et al., 2012, 2013). The mRNA a host to discriminate between pathogenic and apathogenic or
levels of TLR3 are enhanced in MDV-infected lungs (Abdul- attenuated viruses, live or dead pathogens, and also allow coor-
Careem et al., 2009) dination of immunosurveillance. It has been proposed (Vance et
Chicken TLR7 is mostly expressed in lymphoid tissues al., 2009) that in addition to sensing of PAMPs, the host innate
and binds single-stranded RNA (ssRNA) and agonists such as immune system is able to respond to patterns of pathogenesis,
resiquimod (R848) and loxoribine. The functional responses such as sensing pathogen replication and death, cell damage or
to TLR7 agonists vary from up-regulation of type I and II IFN actin cytoskeleton disruption. A simple example is the lack of pro-
to down regulation of IFNs and up-regulation of proinflamma- tection after vaccination with a killed pathogen compared with
tory cytokines (IL-1β and IL-6) and chemokines (CXCLi1 and vaccination with a live pathogen. It will be a challenge to dissect
2) (Philbin et al., 2005; Kogut et al., 2005; Stewart et al., 2012). the immune responses to living pathogens instead of individual
Interestingly, heterophils isolated from different commercial PAMPs, because of the complexity of host pathogen interactions.
broilers responded differently to TLR7 agonists (Kogut et al., TLRs and RLRs recognize viral infections and are essential
2005). The expression of TLR7 is up-regulated after infection by for controlling them. On the other hand, viruses have evolved
IBDV (Rauf et al., 2011a), AIV (Cornelissen et al., 2012, 2013) to escape the host innate immune response. These viral abilities
and MDV (Abdul-Careem et al., 2009). Chicken TLR21 has a to evade host innate immune responses have also been observed
similar function to mammalian TLR9 and binds CpG-ODN. It in most avian viruses and are described in other chapters and
is expressed in lymphoid and non-lymphoid tissues (Browlie et reviewed by Coppo et al., 2013; Haq et al., 2013a; Kapczynski et
al., 2009). In vivo application of IFNα rapidly induces TLR3 and al., 2013.
TLR15, but regulation of TLR21 was not detected. The differen-
tial expression of TLR genes has been found after all major avian Interferons and antiviral effectors
viral infections including MDV, AIV, IBDV, IBV, NDV and will be One of the most potent antiviral pathways that is induced during
described in the respective chapters. the cascade of host responses is the activation of the IFN path-
Other nucleic acids receptors that have been described ways and transcriptional activation of interferon stimulated or
in birds are a family of RNA helicases which includes RIG-I, regulated genes (ISGs/IRGs). Because the vast majority of IRGs
MDA5 and LGP2. In mammals, RIG-I senses in particular are up-regulated they are mostly referred to in the literature as
5′-triphosphorylated or blunt ended double-stranded RNA ISGs. Three families of IFNs have been described in both mam-
(dsRNA) produced during replication of RNA viruses, whereas mals and avian species and, although the IFN systems appear
MDA5 senses long dsRNA. LGP2 has a regulatory capacity, in quite similar, subtle differences are found between mammals and
that it inhibits RIG-I signalling but positively regulates MDA5 between avian species, including the lower number of genes pre-
(Schlee and Hartmann, 2016; Uchikawa et al., 2016). Interest- sent in the genomes of birds. Type I IFNs form a multigene family
ingly, RIG-I has been identified in duck, goose and zebra finch, with closely related IFNα genes and a single IFNβ gene in both
but not in chicken and other Galliformes such as turkeys. The loss humans and chickens. In addition, but less well characterized, are
of RIG-I is however not unique to birds as it was recently reported IFNε, IFNκ, IFNω, IFNδ, IFNτ, and IFNζ (also known as limitin;
missing in the Chinese tree shrew (L. Xu et al., 2016 ). It has reviewed by Hardy et al., 2004). Type II IFN is represented by a
been suggested that the absence of RIG-I makes chickens highly single gene encoding IFNγ. A third family, type III IFNs, was dis-
susceptible to RNA viruses, but the role of sensing short dsRNA covered more recently and includes IFNλ or IL28/29 (Sheppard
has at least in part been taking over by MDA5, suggesting a cer- et al., 2003). In general, IFNα and IFNβ were the first IFNs to be
tain level of plasticity of nucleic acid sensing in the RLR family identified and are best known for their antiviral activity, whereas
members (Hayashi et al., 2014; Uchikawa et al., 2016). Cytosolic IFNγ affects many cells of the immune system and is known for
DNA sensors other than TLR15 and TLR21 have not yet been being a potent activator of macrophages. The activity of IFNλs is
studied in detail in the chicken, but genetic analysis suggests that more restricted to epithelial tissues and is similar to type I IFNs
melanoma 2 (AIM2) is absent, while Z-DNA-binding protein 1 (reviewed by Galani et al., 2015).
(ZBP1) and gamma-interferon-inducible protein Ifi-16 (IFI16)
have not been identified (Cridland et al., 2012). However, given Type I IFN
the current incomplete assembly of the chicken genome and its All type I IFNs are involved in antiviral activities, inhibition of
annotation status (Galgal5), new proteins will continually be cell proliferation, cell differentiation and migration (Hertzog
discovered. For excellent reviews on mammalian PRRs, their and Williams, 2013). To function, IFNα and IFNβ bind to the
regulation and signalling pathways, and viral evasion of PRR sens- common receptor, which is expressed on most cell types, and
ing, the reader is referred to Satoh and Akira, 2016; Luecke and mediate their antiviral properties through induction of ISGs. The
Paludan, 2016; Beachboard and Horner, 2016; Broz et al., 2013; common receptor is a heterodimeric cell surface receptor com-
Aoshi et al., 2011, whereas reviews on avian PRRs have already posed of two chains IFNAR1 and IFNAR2, which upon ligation
been published by Keestra et al., 2013 and Chen et al., 2013. activates the JAK/STAT signalling pathway, phosphorylation of