Submitted to: Viral Immunology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 9/15/2006
Publication Date: 3/2/2007
Citation: Fach, S.J., Meyerholz, D.K., Gallup, J.M., Ackermann, M.R., Lehmkuhl, H.D., Sacco, R.E. 2007. Neonatal Ovine Pulmonary Dendritic Cells Support BRSV Replication with Enhanced IL-4 and IL-10 Gene Transcripts. Viral Immunology. 20(1):119-130. Interpretive Summary: We isolated and identified lung dendritic cells (DCs) in neonatal lambs. Neonatal lung DCs exhibited characteristic morphology when observed by electron microscopy. The neonatal lung DCs are susceptible to bovine respiratory syncytial virus infection and produce proteins that would be ineffective in eliminating the virus. Further studies of these cells should contribute to a better understanding of neonatal susceptibility to certain infections.
Technical Abstract: The lung microenvironment is constantly being exposed to microorganisms and particulate matter. Lung dendritic cells (DCs) play a crucial role in the uptake and processing of antigens found within the respiratory tract. Respiratory syncytial virus (RSV) is a common respiratory tract pathogen in children that induces an influx of DCs to the mucosal surfaces of the lung. Utilizing a neonatal lamb model, we examined the in vivo permissiveness of DCs to RSV infection, as well as overall cell surface changes and cytokine responses of isolated lung DCs after bovine RSV (BRSV) infection. We report that isolated lung DCs and alveolar macrophages support BRSV replication. Isolated lung DCs were determined to be susceptible to BRSV infection as demonstrated by quantification of BRSV NS2 mRNA. BRSV infection induced an initial up-regulation of CD14 expression on lung DCs, but by 5 days post-infection (PI) expression was similar to that on control cells. No significant changes in CD80/86 or MHC class I expression were seen on lung DCs after BRSV infection. Low to moderate expression of MHC class II and DEC-205 was detected by day 5 PI. Initially at day 3 PI, lung DCs from BRSV-infected lambs had decreased endocytosis of FITC-OVA. The amount of FITC-OVA endocytosed by lung DCs isolated at day 5 PI was similar to controls. The most interesting observation was the induction of immunomodulatory IL-4 and IL-10 cytokine gene transcription in lung DCs and AMs after in vivo infection with BRSV. Overall, these findings are the first to demonstrate that neonatal lung DCs support in vivo BRSV replication and produce type II cytokines after viral infection.