Submitted to: Journal of Immunology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 10/3/2006
Publication Date: 12/15/2006
Citation: Loving, C.L., Brockmeier, S., Wenjun, M., Richt, J., Sacco, R.E. 2006. Innate Cytokine Responses in Porcine Macrophage Populations: Evidence for Differential Recongition of dsRNA. Journal of Immunology. 177:8432-8439. Interpretive Summary: The lung is constantly exposed to harmful germs during normal breathing. A key white blood cell in the lung is macrophage. There are macrophages located throughout the body. We find in this study that macrophages taken from different sites in the body respond differently to the same stimulus. This may inluence how these white blood cells respond to germs such as viruses.
Technical Abstract: Pulmonary airways are relatively vulnerable to infection because of continuous exposure to antigen during respiration. The innate, antiviral response must be activated rapidly after pathogen recognition and alveolar macrophages (AM') likely play a role in this response. TLR3 and PKR recognize dsRNA, a replication intermediate of RNA viruses, and initiate the transcription of IFN-a/B. In this study, synthetic dsRNA (polyI:C) was used to investigate innate response of porcine AM' compared to responses of peritoneal macrophages (PM'). PolyI:C triggered production of IFN-a/B in AM' and PM', but levels in AM' were significantly higher. In contrast, mRNA levels of interferon-stimulated genes, Mx and PKR, were significantly higher in PM' than AM'. Low levels of Mx and PKR transcription in AM' was not due to deficient type I interferon receptor (IFNAR) signaling, as exogenous recombinant IFN-a induced nuclear translocation of phosphorylated STAT-1. To investigate the differential mechanism by which IFN-a/B transcription is activated in AM' and PM', 2-aminopurine (2-AP) was used to block dsRNA mediated activation of PKR. IFN-a/B, Mx, and PKR mRNA levels in AM' after polyI:C treatment were unaffected by 2-AP; conversely, transcription of IFN-a/B, Mx, or PKR remained at baseline levels in PM'. Phosphorylated PKR was detected in PM', but not AM', after polyI:C treatment. In addition to IFN-a/B gene induction, mRNA levels of TNF-a and RANTES were significantly greater in AM' than PM' after polyI: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'.