title: Induction of Toll-like receptor 4 signaling in avian macrophages inhibits infectious laryngotracheitis virus replication in a nitric oxide dependent way.
abstract: LPS is one of the pathogen associated molecular patterns that activates Toll-like receptor 4 (TLR4) signaling pathway eliciting antiviral host responses in mammals although information on such responses in avian species is scarce. Our objectives were to characterize the LPS induced innate responses particularly the expression of LPS receptors (TLR4, CD14) in avian macrophages and observe whether TLR4 mediated induction of NO can elicit antiviral response against infectious laryngotracheitis virus (ILTV) replication. We found that LPS was capable of inducing the expression of TLR4, CD14 and NO production but not the type 1 interferons in an avian macrophage cell line, MQ-NCSU. We also showed that TLR4 mediated NO production can lead to antiviral response against ILTV replication when MQ-NCSU cells were treated with LPS and the resultant supernatant was then transferred to ILTV replicating cells to assess antiviral activity. Antiviral activity of NO was blocked by a selective inhibitor, S-methylisothiourea sulfate that inhibits inducible NO synthase. This observation confirms that the antiviral activity is positively correlated with NO production. The data show that LPS can be a potential innate immune stimulant that can be used against ILTV infection in chickens that require further evaluation in vivo.
authors.affiliation: Department of Ecosystem and Public Health, Faculty of Veterinary Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 2Z6, Canada.
authors.forename: Siamak
authors.initials: S
authors.lastname: Haddadi
authors.forename: Dae-Sun
authors.initials: DS
authors.lastname: Kim
authors.forename: Hui
authors.initials: H
authors.lastname: Jasmine
authors.forename: Frank
authors.initials: F
authors.lastname: van der Meer
authors.forename: Markus
authors.initials: M
authors.lastname: Czub
authors.forename: Mohamed Faizal
authors.initials: MF
authors.lastname: Abdul-Careem
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006566:Herpesviridae Infections / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D001352:Herpesvirus 1, Gallid / Q000276:immunology*; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000276:immunology*; D011201:Poultry Diseases / Q000276:immunology / Q000821:virology*; D015398:Signal Transduction / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D007550:Isothiuronium; D009569:Nitric Oxide; C027744:S-methylisothiopseudouronium
keywords: Avian; Infectious laryngotracheitis virus; Lipopolysaccharide; Macrophage; Nitric oxide; Toll-like receptor 4