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          Figure  10.9  Photomicrograph  illustrating  histopathological  changes:  foci  of  acute  hepatic  necrosis  with  heterophil  rich  inflammatory
          infiltrates and the classic large intranuclear basophilic viral inclusions, characteristic features of inclusion body hepatitis (IBH). H&E, 400 ×
          magnification. Courtesy of Dr Marina Brash, Animal Health Laboratory, University of Guelph.

          1998;  Pierson  and Fitzgerald,  2013;  Dhama et al.,  2017).  The   effects on cells of the adaptive immune system (de Waal Malefyt,
          microscopic lesions are most evident in the intestinal tract and in   1991). IL-8 is expressed by activated macrophages and secreted
          the immune system. In the spleen, hyperplasia of white pulp and   to recruit immune cells, mainly neutrophils, to the site of infec-
          lymphoid necrosis are seen. Cowdry type B intranuclear inclusion   tion (Modi et al., 1990). IL-18 is also produced in macrophages
          bodies in the lympho-reticular cells can be observed (Saunders et   and stimulates NK and certain T-cells to release IFN-γ (Biet et
          al., 1993; Suresh and Sharma, 1996). Lymphoid necrosis in the   al., 2002).
          bursa of Fabricius and thymus have been described (Hussain et   Upon  infection  with FAdV-4  (ON1  isolate),  transcription
          al., 1993; Suresh and Sharma, 1995). The typical lesions of the   levels of IFNγ and IL-10 are significantly higher in liver at 3 dpi,
          intestinal tract include congestion of the mucosa, haemorrhage of   whilst levels of IL-8 and IL-18 remain unchanged. IFNγ and IL-18
          tips of the villi and necrosis. Inclusions bodies can also be found   mRNA levels in spleen are significantly lower in FAdV-4 infected
          in a variety of organs (Itakura and Carlson, 1975; Meteyer et al.,   birds at 10 dpi, whilst their levels remain nearly unchanged in
          1992; Trampel et al., 1992).                          caecal tonsils (Grgić et al., 2013a).
                                                                   Upon FAdV-8 infection, transcription of IFN-γ and IL-10
                                                                is up-regulated and down-regulated, respectively, in spleen of
          Immune response                                       birds at 3 dpi. IL-18 expression in spleen is up-regulated at 1 dpi
                                                                and down-regulated at 7 dpi. IL-8 expression seems to remain
          Innate immunity                                       unchanged until 7 dpi, time after which the expression of this
          Studies on the innate immunity in response to avian adenovirus   cytokine is significantly down-regulated up to 10 dpi. In caecal
          infections are limited. In general, type I IFNs and pro-inflammatory   tonsils, IFN-γ, IL-18 and IL-10 mRNA levels are increased at 1
          cytokines are rapidly expressed in response to infection to limit   dpi, though their levels do not differ significantly with respect to
          virus replication and stimulate the acquired immunity.  those from uninfected birds. IL-8 expression seems to be down-
            Infections with FAdV-4, FAdV-8 and FAdV-9, and likely all   regulated, but its levels seem not to differ significantly to those
          aviadenoviruses, up-regulate the expression of type I and II   from controls. In liver, IFN-γ is significantly up-regulated at 3, 5,
          IFNs (IFN-α and IFNγ, respectively) in all studied tissues such   and 7 dpi. IL-10 is also found up-regulated in infected chickens at
          as liver, caecal tonsil, spleen and bursa of Fabricius, whilst the   1, 3, and 5 dpi. Expression levels of IL-8 and IL-18 significantly
          expression of other cytokines (IL-10, IL-8 and IL-18) seems to   increase at 3 dpi, while IL-8 seems to decrease at 5, 7, and 10 dpi
          be  tissue-dependent  (Deng et al.,  2013;  Grgić et al.,  2013a,b).   (Grgić et al., 2013b).
          IFNγ is an essential cytokine for innate and adaptive immunity   IFN-α, IFNγ and IL-12 mRNAs are up-regulated in liver of
          against pathogens including viruses. This cytokine is produced   FAdV-9-infected chickens. IFN-α is detected at 3, 5 and 7 dpi
          by NK and natural killer T (NKT) cells as well as by activated   and declines by 14 dpi, whilst levels of IFNγ mRNA is detected
          CD4 Th1 and CD8 T-cells (Schoenborn and Wilson, 2007).   at 3 and 5 dpi and remain significantly high up to 14 dpi. IL-12
          IL-10 has both immunosuppressive and immunostimulating   is found up-regulated at 3, 5, 7 and 14 dpi. IL-10 mRNA levels
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