Submitted to: Keystone Symposia
Publication Type: Abstract Only
Publication Acceptance Date: September 28, 2004
Publication Date: January 8, 2005
Citation: He, H., Kogut, M.H. 2005. Expression of toll-like receptors and differential activation of nitric oxide synthase by toll-like receptor agonists in monocytes from neonatal chicken [abstract]. Innate Immunity to Pathogens Keystone Symposium. p. 49. Technical Abstract: Toll-like receptors (TLRs) play a major role in the innate immune system for initial recognition of microbial pathogens and pathogen associated components. Nitric oxide (NO) is generated in immune cells, such as monocytes and macrophages, in response to microbial stimulation and is involved in pathogenesis and control of infection. We used RT-PCR analysis to examine the TLR expression profile on chicken monocytes and demonstrated these cells express chicken TLR2, 3, 4, 6, and 7, but not TLR5. We also investigated the differential induction of NO synthesis in chicken peripheral blood monocytes by TLR agonists, including flagellin (from Salmonella typhimiurum, FGN), synthetic lipoprotein Pam3CSK4 (PAM), lipopolysaccharide (from Salmonella enteritidis, LPS), lipoteichoic acid (from Staphylococcus aureus, LTA), the synthetic double stranded RNA analog (poly I:C), the guanosine analog, loxoribine (LOX), and synthetic CpG oligodeoxydinucleotide (CpG-ODN). Our results indicated that there was a vast difference among those agonists for their ability to induce NO production. CpG-ODN and LPS were found to be the most potent stimuli and induced significant quantities of NO in cultured monocytes, whereas LTA only stimulated significant NO production at high concentrations. Other agonists such as FGN and poly I:C stimulated very little NO, while PAM, LOX, and nCpG-ODN (control ODN) did not induce NO production. RT-PCR analysis demonstrated that LPS, LTA, and CpG-ODN induced iNOS expression in monocytes; whereas the other agonists did not. The presence of TLRs on chicken monocytes and the differential induction of NO production in chicken monocytes by various TLR agonists suggest the differentiation of signaling pathways downstream of individual TLRs.