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Title: Differential Expression of Ovine Innate Immune Genes by Preterm and Neonatal Lung Epithelia Infected with Respiratory Syncytial Virus

Author
item KAWASHIMA, KENJI - IOWA STATE UNIVERSITY
item MEYERHOLZ, DAVID - IOWA STATE UNIVERSITY
item GALLUP, JACK - IOWA STATE UNIVERSITY
item GRUBOR, BRANKA - IOWA STATE UNIVERSITY
item LAZIC, TATJANA - IOWA STATE UNIVERSITY
item Lehmkuhl, Howard
item ACKERMANN, MARK - IOWA STATE UNIVERSITY

Submitted to: Viral Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/27/2006
Publication Date: 6/9/2006
Citation: Kawashima, K., Meyerholz, D.K., Gallup, J.M., Grubor, B., Lazic, T., Lehmkuhl, H.D., Ackermann, M.R. Differential Expression of Ovine Innate immune Genes by Preterm and Neonatal Lung Epithelia Infected with Respiratory Syncytial Virus. Viral Immunology. 19(2):316-323.

Interpretive Summary: Preterm human infants have increased susceptibility to severe manifestations of respiratory syncytial virus (RSV) infection. In sheep, RSV disease severity has similar age-dependent characteristics and sheep are born with several related immune processes similar to humans making them a valuable model to study lung infection by this important respiratory virus. In this study, the effect of RSV infection on expression of these immune genes was determined for bovine RSV-infected cells from the respiratory tract. Control lambs had increased expression of innate immune molecules in full term compared to preterm cells. Generally, RSV infected cells had consistently higher gene expression for immune levels in both pre and post term lambs. This study defines specific innate immune components that have differential age-dependent expression in the airway epithelia. These gene expression results provide a framework for future studies on age-dependent susceptibility to RSV and RSV pathogenesis.

Technical Abstract: Preterm infants have increased susceptibility to severe manifestations of respiratory syncytial virus (RSV) infection. The cause(s) for this age-dependent vulnerability is/are not well-defined, but alterations in innate immune products have been implicated. In sheep, RSV disease severity has similar age-dependent characteristics and sheep have several related innate molecules for study during pulmonary infection including surfactant protein A (SP-A), surfactant protein D (SP-D), sheep beta defensin1 (SBD1), monocyte chemotactic protein 1 (MCP1), and Toll-like receptor 4 (TLR4). However, the in vivo cellular gene expression as a response to RSV infection is poorly understood. In this study, the effect of RSV infection on expression of these innate immune genes was determined for bovine RSV-infected (bRSV + fluorescence) epithelial cells, adjacent cells lacking bRSV antigen (adjoining cells lacking fluorescence), and control cells from non-infected lung using laser capture microdissection (LCM) and real-time RT-PCR. Control lambs had increased expression of innate immune molecules in full term (term) compared to preterm epithelia with statistical significance in SBD1, SP-D, and TLR4 mRNA. Infected cells (bRSV + fluorescent cells) had consistently higher mRNA levels of SP-A (preterm and term), MCP1 (preterm and term), and SP-D (preterm). Interestingly, bRSV - cells of infected term lambs had significantly reduced SP-D mRNA expression compared to bRSV + and control epithelia, suggesting that RSV infected cells may regulate the adjacent epithelial SP-D expression. This study defines specific innate immune components (e.g., SBD1, SP-D, and TLR4) that have differential age-dependent expression in the airway epithelia. Furthermore, cellular bRSV infection enhanced certain innate immune components while suppressing adjacent cellular SP-D expression in term animals. These in vivo gene expression results provide a framework for future studies on age-dependent susceptibility to RSV and RSV pathogenesis.