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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 - SCHICHINOHE RESEARCH UNIT
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: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 8/2/2006
Publication Date: 10/9/2006
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 [abstract]. Veterinary Comparative Respiratory Meeting, October 9-10, 2006, Jena, Germany. p. 1.

Interpretive Summary:

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 defensin 1 (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.