FUNCTIONAL GENOMICS AND GENETIC ANALYSIS OF THE INNATE IMMUNE RESPONSE REQUIRED TO RESIST FOOD-BORNE BACTERIAL INFECTIONS IN POULTRY
Location: Food and Feed Safety Research
Title: Differential mRNA expression of the avian-specific toll-like receptor 15 between heterophils from Salmonella-susceptible and -resistant chickens
Research conducted cooperatively with:
| Cobb-Vantress, Inc.|
Submitted to: Immunogenetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 23, 2008
Publication Date: January 10, 2009
Citation: Nerren, J.R., Swaggerty, C.L., MacKinnon, K.M., Genovese, K.J., He, H., Pevzner, I., Kogut, M.H. 2009. Differential mRNA expression of the avian-specific toll-like receptor 15 between heterophils from Salmonella-susceptible and -resistant chickens. Immunogenetics. 61:71-77.
Interpretive Summary: Host immune cells recognize unique components of bacteria using structures located on their surface called pattern recognition receptors (PRRs). These PRRs then send signals to the brain of the cell, the nucleus, which causes the cell to respond in a defensive manner. Toll-like receptors (TLRs) are a family of PRR and have been shown to play an important role in the immune system's defense against bacteria, fungi, and viruses. These receptors function with the help of proteins called adaptor proteins. In the present study, immune cells from Salmonella-susceptible and -resistant chickens were stimulated with Salmonella enteritidis. Levels of mRNA (a molecule that is translated into protein) for TLRs 4, 5, and 15, and adaptor proteins MyD88, TIRAP, and TRIF were measured. Following this stimulation the immune cells responded by increasing their production of mRNA specific for the receptor TLR 15, but not for TLRs 4 and 5, or the adaptor proteins MyD88, TIRAP, or TRIF. In addition, immune cells from Salmonella-resistant chickens had significantly higher levels of TLR 15 mRNA production than immune cells from Salmonella-susceptible chickens. Results from this study suggest that the chicken-specific TLR 15 may play a role in the innate immune response of chickens to infection with Salmonella.
Pattern recognition receptors (PRRs) are essential for recognition of conserved molecular constituents found on infectious microbes. Toll-like receptors (TLRs) are a critical component of the PRR repertoire and are coupled to downstream production of cytokines, chemokines, and antimicrobial peptides by TLR adaptor proteins. Our laboratory recently demonstrated a potential role for TLR function in the differential innate response of two distinct lines of chickens to bacterial infections. The aim of the present study is to elucidate the role of TLRs in the differential innate responsiveness by measuring differences between lines A (resistant) and B (susceptible) in heterophil mRNA expression of selected TLRs (TLRs 4, 5, and 15) and TLR adaptor proteins (MyD88, TRIF, and TIRAP). We employed real-time quantitative PCR to measure changes in gene expression by heterophils in response to stimulation with Salmonella enterica serovar Enteritidis (SE). Although heterophils from both lines of chickens had significantly increased expression of TLR 15 mRNA in response to stimulation with SE, heterophils from chickens resistant to infection with SE had significantly greater levels of TLR 15 mRNA expression prior to and following stimulation with SE than heterophils from chickens susceptible to infection with SE. No significant differences were noted between lines in non-stimulated levels of TIRAP, but upon SE-stimulation line A birds had higher levels of expression than B birds. No significant differences were found in heterophils between lines for mRNA expression of TLRs 4 and 5 nor MyD88, and TRIF. These data indicate that differences in the gene expression of TLR 15 by heterophils likely accounts for some of the observed differences between the lines in their susceptibility to infection.