Room: CW 326, Biological Sciences
Phone: (780) 492-5498
Fax: (780) 492-9234
Christine Mesa-collecting blood from wild mallards
Antiviral pattern recognition receptors of ducks.
Detection of viral RNA by TLR7 is essential for interferon-alpha production by plasmacytoid dendritic cells in response to influenza virus. To determine the function of duck TLR7, we tested whether duck cells could respond to TLR7 ligands. Stimulation of duck immune cells with TLR7 agonists efficiently upregulated genes encoding proinflammatory cytokines and interferon-alpha (IFNα). It is very significant that the TLR7 pathway to interferon-alpha production is intact in ducks, since it does not always work in chickens (MacDonald et al., 2008).
Ducks, but not chickens, have a functional influenza sensor RIG-I that contributes to the innate immune response to influenza.
We showed by bioinformatics and Southern blotting that chickens do not have the RIG-I gene. We showed that duck RIG-I is functional in chicken embryonic fibroblast DF-1 cells (a spontaneously immortalized chicken cell line) and confers detection of RIG-I ligand (Barber et al., 2010). This provides a simple explanation for why ducks are resistant to strains of flu that would kill chickens in a few days. Now our goal is to understand how RIG-I is regulated in an influenza infection in ducks (Domingo Miranzo Navarro, PDF).
Immune gene discovery through genomics projects
We use expressed sequence tag (EST) projects to discover immune relevant genes (Xia et al., 2007). We are particularly interested in genes that allow us to manipulate dendritic cell function, since this is key to successful vaccination. Two ESTs encoded DCIR and DCAR. DCIR is an endocytic receptor on dendritic cells that influences antigen presentation. The closest mammalian homologue of DCAR is BDCA-2, which controls the interferon response. We have sequenced a duck genomic clone containing DCIR, and two DCAR genes to clarify the identity of the genes and examine the evolutionary history of the locus (Guo et al., 2008).
Two ESTs encoded CCL19 and CCL21, homologues of mammalian chemokines involved in the recruitment of na´ve lymphocytes and dendritic cells to lymphoid tissues. We showed that CCL19/21 expression is upregulated in influenza-infected tissues and absent in the putative duck lymph nodes (Fleming-Canepa et al., 2011).
Genes expressed in antiviral defenses against highly pathogenic avian influenza.
In an international collaboration, we will compare genes expressed in response to highly pathogenic avian influenza versus low pathogenic strains using high throughput 454 platform sequencing and differential subtractive screening. Expression of selected genes involved in antiviral responses will be characterized by real-time PCR (Hillary Vanderven, MSc). Candidate antiviral genes will be tested for function (Alysson Blaine, MSc candidate, Graham Blyth, Zubair Mohammad, Honours students).
Last Modified:2011-09-30 |