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Title:   Author  item
                                            He, Louisitem
                                            Genovese, Kenneth

                                                         - *Ken*item
                                            Nisbet, Daviditem
                                            Kogut, Michael

                                                         - *Mike*
  Submitted to: Molecular Immunology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 7/6/2005
                                    Publication  Date: 1/4/2006
                                    Citation: He, H., Genovese, K.J., Nisbet, D.J., Kogut, M.H. 2006. Profile of toll-like receptor expressions and induction of nitric oxide synthesis by toll-like receptor agonists in chicken monocytes. Molecular Immunology. 43:783-789.Interpretive Summary: Toll-like receptors are protein molecules that are produced by animals to detect bacteria and fight infections.  Those protein molecules are very important because they control the body's immune responses to bacterial infection.  A chicken white blood cell called the monocyte can produce bacterial-killing chemicals.  This bacteria-killing mechanism helps chickens fight bacterial infections and stay healthy.  We found that the chicken monocyte can produce Toll-like receptors.  These Toll-like receptors, in turn, help the chicken monocytes produce bacteria-killing chemicals when they are exposed to the bacteria and chemicals made by bacteria.  Our findings are important to the veterinary medicine and pharmaceutical industries in the United States because they show that we can possibly stimulate Toll-like receptors of baby chick monocytes to fight bacterial infections more efficiently.
                                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 expression of inducible nitric oxide synthase in monocytes while 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.


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