title: Diacylated lipopeptide from Mycoplasma synoviae mediates TLR15 induced innate immune responses.
abstract: Avian-specific toll like receptor 15 (TLR15) is functionally equivalent to a group of TLR2 family proteins that the mammalian innate immune system utilizes to recognize a broad spectrum of microbe-associated molecular patterns, including bacterial lipoproteins. In this study we examined the role of chicken TLR2 family members in the innate immune response to the avian pathogenic bacterium, Mycoplasma synoviae. We found that Mycoplasma synoviae, and specifically the N-terminal diacylated lipopeptide (MDLP) representing the amino-terminal portion of its mature haemagglutinin protein, significantly induces the expression of TLR15, but not TLR1 and TLR2 in chicken macrophages and chondrocytes. TLR15 activation is specific and depends on diacylation of the lipopeptide. Activation of TLR15 after stimulation with Mycoplasma synoviae and MDLP triggers an increase in the expression of transcription factor nuclear factor kappa B and nitric oxide production. Moreover, transfection of avian macrophage cells with small interfering RNA reduces the expression of TLR15 after stimulation with MDLP. This leads to decreased activation of the innate immune response, as measured by nitric oxide production. Additionally, pretreatment of cells with neutralizing anti-TLR15 antibody results in a notable attenuation of MDLP-driven release of nitric oxide. This positive correlation may constitute a mechanism for stimulating the innate immune response against avian mycoplasmas in chicken cells via TLR15.
authors.forename: Irena
authors.initials: I
authors.lastname: Oven
authors.forename: Katarina
authors.initials: K
authors.lastname: Resman Rus
authors.forename: Daliborka
authors.initials: D
authors.lastname: Dušanić
authors.forename: Dušan
authors.initials: D
authors.lastname: Benčina
authors.forename: Calvin L
authors.initials: CL
authors.lastname: Keeler
authors.affiliation: Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Groblje 3, SI-1230 DomŽale, Slovenia. mojca.narat@bf.uni-lj.si.
authors.forename: Mojca
authors.initials: M
authors.lastname: Narat
mesh_terms: D000215:Acylation; D000818:Animals; D030161:Avian Proteins / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002645:Chickens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate; D008024:Ligands; D055666:Lipopeptides / Q000235:genetics* / Q000378:metabolism; D009175:Mycoplasma Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000662:veterinary; D045805:Mycoplasma synoviae / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011201:Poultry Diseases / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D051194:Toll-Like Receptor 1 / Q000235:genetics / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics* / Q000378:metabolism
chemical_list: D030161:Avian Proteins; D001426:Bacterial Proteins; D008024:Ligands; D055666:Lipopeptides; D016328:NF-kappa B; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D009569:Nitric Oxide