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Differential expression of ovine innate immune genes by preterm and neonatal lung epithelia infected with respiratory syncytial virus
Journal article   Open access   Peer reviewed

Differential expression of ovine innate immune genes by preterm and neonatal lung epithelia infected with respiratory syncytial virus

Kenji Kawashima, David K Meyerholz, Jack M Gallup, Branka Grubor, Tatjana Lazic, Howard D Lehmkuhl and Mark R Ackermann
Viral immunology, Vol.19(2), pp.316-323
2006
DOI: 10.1089/vim.2006.19.316
PMCID: PMC2791066
PMID: 16817774
url
https://doi.org/10.1089/vim.2006.19.316View
Published (Version of record) Open Access

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.
Animals, Newborn Epithelial Cells - metabolism Sheep Diseases - virology Premature Birth - veterinary RNA, Messenger - genetics Immunity, Innate - genetics Lung - cytology RNA, Messenger - metabolism Respiratory Syncytial Virus Infections - immunology Sheep Diseases - immunology Lung - virology Microdissection - methods Animals Gene Expression Regulation, Developmental Lasers Epithelial Cells - immunology Epithelial Cells - virology Sheep Respiratory Syncytial Virus Infections - veterinary Respiratory Syncytial Virus Infections - virology Respiratory Syncytial Viruses - pathogenicity

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