[show abstract][hide abstract] ABSTRACT: The mechanisms of disease severity caused by H5N1 influenza virus infection remain somewhat unclear. Studies have indicated that a high viral load and an associated hyper inflammatory immune response are influential during the onset of infection. This dysregulated inflammatory response with increased levels of free radicals, such as nitric oxide (NO), appears likely to contribute to disease severity. However, enzymes of the nitric oxide synthase (NOS) family such as the inducible form of NOS (iNOS) generate NO, which serves as a potent anti-viral molecule to combat infection in combination with acute phase proteins and cytokines. Nevertheless, excessive production of iNOS and subsequent high levels of NO during H5N1 infection may have negative effects, acting with other damaging oxidants to promote excessive inflammation or induce apoptosis.
There are dramatic differences in the severity of disease between chickens and ducks following H5N1 influenza infection. Chickens show a high level of mortality and associated pathology, whilst ducks show relatively minor symptoms. It is not clear how this varying pathogenicty comes about, although it has been suggested that an overactive inflammatory immune response to infection in the chicken, compared to the duck response, may be to blame for the disparity in observed pathology. In this study, we identify and investigate iNOS gene expression in ducks and chickens during H5N1 influenza infection. Infected chickens show a marked increase in iNOS expression in a wide range of organs. Contrastingly, infected duck tissues have lower levels of tissue related iNOS expression.
The differences in iNOS expression levels observed between chickens and ducks during H5N1 avian influenza infection may be important in the inflammatory response that contributes to the pathology. Understanding the regulation of iNOS expression and its role during H5N1 influenza infection may provide insights for the development of new therapeutic strategies in the treatment of avian influenza infection.
PLoS ONE 01/2011; 6(1):e14561. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Although Toll-like receptors (TLRs) have been well characterised in mammals, less work has been carried out in non-mammalian species, such as chickens. In this study the response of chicken cells to the TLR9 subfamily of ligands was characterised in vitro and in ovo. It was found that even though chickens appear to have only one functional receptor to represent the TLR9 subfamily, stimulation of chicken splenocytes with TLR7 and TLR9 ligands induced proinflammatory cytokine production and cell proliferation, similar to that observed when the homologous mammalian receptors are stimulated. Furthermore, we demonstrated that the in ovo administration of these TLR ligands elicits a response, such as cytokine production, that can be detected post-hatch. The current knowledge of the action of TLR ligands in mammals, in conjunction with their immunomodulating ability shown in this study, draws attention to their potential use as therapeutic agents for the poultry industry.
Developmental and comparative immunology 01/2009; 33(5):660-7. · 3.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: Viral infections in chickens pose a major health threat to the poultry industry. Infectious bronchitis virus (IBV) usually causes respiratory disease; however, the disease severity is influenced by the genotype of the chicken and the IBV strain involved. Nephropathogenic strains of IBV, such as the Australian T strain, can cause high mortalities due to kidney failure characterized by mononuclear cell infiltration and inflammation. In a previous study, a line of specific pathogen-free chickens, the S-line, was shown to be susceptible to high mortalities from IBV infection. The cause of these high mortalities is unknown but it is suspected that differential cytokine expression may play a role. With this in mind, we decided to study the role of the proinflammatory cytokine interleukin (IL)-6 during infection to determine its contribution to nephritis and influence on disease susceptibility. To investigate this, we infected the susceptible S-line and the more disease-resilient HWL line with the T strain of IBV and measured their cytokine response levels. In both lines of birds, IL-6 mRNA levels were elevated in the kidneys at 4 d postinfection. However, in S-line chickens, these levels were 20 times higher than those in the HWL chickens. In addition, S-line birds also showed three times higher serum IL-6 levels than HWL birds after IBV infection. These findings suggest that IL-6 may play a role in IBV-induced nephritis and may open an avenue to develop alternative strategies, such as the use of antiinflammatory cytokines, to overcome the nephropathogenic effects of IBV.
[show abstract][hide abstract] ABSTRACT: The worldwide trend towards a reduced reliance on in-feed antibiotics has increased the pressure to develop alternative strategies to manage infectious diseases in poultry. With this in mind, there is a great emphasis on vaccine use and the enhancement of existing vaccines to provide long-term protection. Currently existing adjuvants for poultry can have deleterious side-effects, such as inflammation, resulting in the down-grading of meat quality and a subsequent reduction in profits. Therefore, to enhance the use of vaccination, alternative adjuvants must be developed. The use of recombinant cytokines as adjuvants in poultry is attracting considerable attention, and their potential role as such has been addressed by several studies. The recent identification of a number of chicken cytokine genes has provided the possibility to study their effectiveness in enhancing the immune response during infection and vaccination. This review focuses on the recent studies involving the assessment of cytokines as vaccine adjuvants.
Immunology and Cell Biology 01/2005; 82(6):638-43. · 3.93 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cytokines, as immune activators, have been investigated in mammalian systems as natural adjuvants and therapeutics. In particular, interleukin-2 (IL-2) has been studied widely as a vaccine adjuvant and immuno-enhancer because of its role in activating T cell proliferation. We show here that the first nonmammalian IL-2 gene cloned, chicken IL-2 (ChIL-2), exhibits similar biologic activities to those of mammalian IL-2. To assess the activities of ChIL-2 in vivo, we injected birds with recombinant ChIL-2 (rChIL-2) protein. rChIL-2 treatment induced peripheral blood lymphocytes to express cell surface IL-2 receptors (IL-2R) within 48 h and resulted in an increase in the proportion of peripheral blood CD4+ and CD8+ T cells. Using bromodeoxyuridine (BrdU) incorporation as a measurement of cell proliferation, we showed the increase in T cell populations to be due to cell proliferation. The ability of ChIL-2 to cause both activation and proliferation of T cells in vivo indicates that it has the potential to be used as an immune activator.
Journal of Interferon & Cytokine Research 08/2002; 22(7):755-63. · 3.30 Impact Factor