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,
* Immunobiology Graduate Program,
Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011; and
Respiratory Diseases Research Unit and
Virus and Prion Diseases Research Unit, U.S. Department of Agriculture/Agricultural Research Service, National Animal Disease Center, Ames, IA 50010
Pulmonary airways are vulnerable to infection because of exposure to Ag during respiration. The innate, antiviral response must be activated rapidly after pathogen recognition, and alveolar macrophages (AM
) play a role in this response. TLR3 and protein kinase R (PKR) recognize dsRNA, a replication intermediate of RNA viruses, and initiate transcription of IFN-
. In this study, synthetic dsRNA poly(I:C) was used to investigate innate responses of porcine AM compared with responses of peritoneal macrophages (PM). Poly(I:C) triggered IFN- in AM and PM, but levels in AM were higher. In contrast, mRNA levels of IFN-stimulated genes, Mx and PKR, were greater in PM than AM. Low levels of Mx and PKR transcription in AM were not due to deficient type I IFN receptor signaling, as exogenous IFN- induced nuclear translocation of phosphorylated STAT1. To investigate the differential mechanism by which IFN- transcription is activated in AM and PM, 2-aminopurine (2-AP) was used to block dsRNA-mediated activation of PKR. IFN-, Mx, and PKR mRNA levels in AM after poly(I:C) treatment were unaffected by 2-AP; conversely, transcription of IFN-, Mx, or PKR remained at baseline levels in PM. Phosphorylated PKR was detected in PM, but not AM, after poly(I:C) treatment. In addition to IFN- gene induction, mRNA levels of TNF- and RANTES were higher in AM than PM after poly(I:C) stimulation. In summary, differential dsRNA-induced cytokine expression patterns between AM and PM provide evidence that dsRNA recognition and subsequent signaling is likely mediated via TLR3 in AM and PKR in PM.
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1 Address correspondence and reprint requests to Dr. Randy E. Sacco, Respiratory Diseases of Livestock Research Unit, National Animal Disease Center, U.S. Department of Agriculture/Agricultural Research Service, 2300 Dayton Road, Ames, IA 50010. E-mail address: rsacco{at}nadc.ars.usda.gov
2 Abbreviations used in this paper: AM, alveolar macrophage; M, macrophage; PM, peritoneal M; PAMP, pathogen-associated molecular pattern; PKR, protein kinase R; VSV, vesicular stomatitis virus; IFNAR, type I IFN receptor; 2-AP, 2-aminopurine; ISG, IFN-stimulated gene; rpIFN, recombinant porcine IFN; IRF, IFN regulatory factor; TRIF, Toll/IL-1R domain-containing adapter-inducing IFN-; SOCS, suppressors of cytokine signaling.
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