Article

Expression of select immune genes (surfactant proteins A and D, sheep beta defensin 1, and toll-like receptor 4) by respiratory epithelia is developmentally regulated in the preterm neonatal lamb.

Department of Veterinary Pathology, 2740 College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA.
Developmental & Comparative Immunology (Impact Factor: 3.71). 02/2006; 30(11):1060-9. DOI: 10.1016/j.dci.2006.01.001
Source: PubMed

ABSTRACT Preterm infants experience enhanced susceptibility and severity to respiratory syncytial virus (RSV) infection. Terminal airway epithelium is an important site of RSV infection and the extent of local innate immune gene expression is poorly understood. In this study, expression of surfactant proteins A and D (SP-AD), sheep beta defensin 1 (SBD1), and toll-like receptor 4 (TLR4) mRNA were determined in whole lung homogenates from lambs. SP-AD and TLR4 mRNA expression increased (p < 0.05) from late gestation to term birth. In addition, gene expression of LCM-retrieved type II pneumocytes (CD208+), adjacent epithelium (CD208-) and bronchial epithelium demonstrated that bronchiole-alveolar junction epithelium (combined CD208 +/-) had significant (p < 0.05) developmental increases in SP-AD, SBD1 and TLR4 mRNA, whereas CD208+ cells had statistically significant increases only with SP-A mRNA. Using immunofluorescence, SP-AD antigen distribution and intensity were also greater with developmental age. These studies show reduced SBD1, SP-AD, and TLR4 expression in the preterm lung and this may underlie enhanced RSV susceptibility.

0 Followers
 · 
63 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Preterm birth is a risk factor for respiratory syncytial virus (RSV) bronchiolitis and hospitalization. The pathogenesis underlying this is not fully understood, and in vivo studies are needed to better clarify essential cellular features and molecular mechanisms. Such studies include analysis of lung tissue from affected human infants and various animal models. The preterm and newborn lamb lung has developmental, structural, cellular, physiologic, and immunologic features similar to that of human infants. Also, the lamb lung is susceptible to various strains of RSV that infect infants and cause similar bronchiolar lesions. Studies in lambs suggest that viral replication in airways (especially bronchioles) is extensive by 4 days after infection, along with bronchiolitis characterized by degeneration and necrosis of epithelial cells, syncytial cell formation, neutrophil infiltration, epithelial cell hypertrophy and hyperplasia, and innate and adaptive immune responses. RSV bronchiolitis greatly affects airflow and gaseous exchange. RSV disease severity is increased in preterm lambs compared with full-term lambs; similar to human infants. The lamb is conducive to experimental assessment of novel, mechanistic therapeutic interventions such as delivery of vascular endothelial growth factor and enhancement of airway epithelial oxidative responses, Club (Clara) cell protein 10, and synthesized compounds such as nanobodies. In contrast, exposure of the fetal ovine lung in vivo to ethanol, a risk factor for preterm birth, reduces pulmonary alveolar development and surfactant protein A expression. Because the formalin-inactivated RSV vaccination enhances some inflammatory responses to RSV infection in lambs, this model has the potential to assess mechanisms of formalin-inactivated RSV enhanced disease as well as newly developed vaccines.
    ILAR journal / National Research Council, Institute of Laboratory Animal Resources 06/2014; 55(1):4-15. DOI:10.1093/ilar/ilu003 · 1.05 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Damage-associated molecular patterns (DAMPs) and antimicrobial peptides (AMPs) are components of pulmonary innate immunity and tissue repair. We hypothesized that DAMPs and AMPs would increase in response to fetal pulmonary inflammation caused by chorioamnionitis in a time-dependent manner. Methods: Fetal sheep were exposed to intra-amniotic saline or LPS (10mg) between 5 hours and 15 days prior to preterm delivery at 125±2 days. Lung tissue mRNAs for proinflammatory cytokines; AMPs: myeloid antimicrobial peptide-29 (MAP29), dodecapeptide, sheep beta-defensin-1 (SBD1), sheep beta-defensin-2 (SBD2); DAMPs: IL-1α, lactoferrin, heat-shock protein-70 (HSP70), high-mobility group box protein-B1 (HMGB1), receptor for advanced glycation endproducts (RAGE) were measured by RTqPCR. Immunohistochemistry of DAMPs and in situ hybridization of AMPs was performed. Results: IL-1α, IL-1β, IL-6, IL-8, IL-10, MCP-1, and TNF-α mRNA increased after LPS exposure. MAP29, dodecapeptide, SBD1 and SBD2 mRNA were suppressed at 24 hours. MAP29 and dodecapeptide mRNA then increased at 8 days. Lactoferrin increased at 24 hours. There were no changes for HMGB1, HSP70 or RAGE. MAP29 and dodecapeptide localized to alveolar cells, increased 8 days after exposure to LPS. Conclusion: AMPs are initially suppressed in the fetal lung by LPS-induced chorioamnionitis. The late induction of MAP29 and Dodecapeptide may be related to lung repair.
    Pediatric Research 08/2014; 76(5). DOI:10.1038/pr.2014.113 · 2.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Toll-like receptors (TLRs), important components of innate immune response, play a pivotal role in early recognition of pathogen as well as in the initiation of robust and specific adaptive immune response. In the present study, the expression profile of chicken TLRs (TLR2A, TLR3, TLR4, TLR5, TLR7, TLR15, and TLR21) in various chicken embryonic tissues during embryo development was examined by real-time PCR assay. All the TLR mRNAs were expressed in whole embryonic tissue as early as 3rd embryonic day (ED). Four of the seven TLRs (TLR2, TLR3, TLR4, and TLR7) mRNA expressions were significantly (P < 0.01) higher at 12ED relative to expression at 3 ED, whereas TLR15 mRNA expression was significantly (P < 0.01) higher on 7ED and TLR5 and 21 were highly expressed on 18 ED. Among all the TLRs investigated TLR4 mRNA was the highest expressed and TLR15 mRNA expression was the lowest in all tissues during chicken embryo development. Tissue wise analysis of mRNA expression of TLRs showed that liver expressed significantly (P < 0.01) higher levels of most of the genes (TLR2, TLR4, and TLR21). However no significant difference was found in TLR15 mRNA expression among the tissues during development. Our results suggest the innate preparedness of chicken embryos and also a possible role for TLRs in the regulation of chicken embryo development that needs to be further evaluated.
    Animal Biotechnology 04/2015; 26(2):130-135. DOI:10.1080/10495398.2014.939658 · 0.64 Impact Factor

Full-text (2 Sources)

Download
120 Downloads
Available from
May 22, 2014