Pathogenomic approaches to characterizing the avian host innate immune response to microbial infection

Abstract

The avian innate immune response is activated within hours of infection. While it is difficult to prevent infection by a pathogen, clinical signs of disease can be ameliorated once the host-pathogen interactions are elucidated. Host-pathogen interaction research has predominantly focused on the adaptive immune response and cell signaling events later in infection; recently however, the innate immune response and early signaling events have garnered increased attention as another area worthy of investigation and intervention. Cells of innate immunity serve as the first-responders to infection, their signaling and antigen presentation is critical to the development of a protective adaptive immune response, and the cellular products of their activity (cytokines, reactive oxygen species, complement, etc.) are responsible for many of the clinical signs associated with disease. ☐ Avian immunology research is expanding quickly due to the growing knowledge base of the chicken cytokines, Toll-Like Receptors (TLRs) and their immune signaling pathways. Our aim was characterize the avian innate immune response to microbial infection by utilizing a pathogenomics approach. By performing microarray experiments using our Avian Innate Immune Microarray (AIIM), we were able to measure the transcriptional host immune response to several important avian pathogens. Furthermore, by performing immunotherapeutic interventions using TLR agonists prior to challenge with highly pathogenic avian influenza virus, we were able to extend survival time of treated birds by 14% (p<0.01). This project has led to the characterization of the avian innate immune in different avian species, to different pathogens, at early time points throughout infection, and with and without the aid of a pre-treatment.