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: 2.82). 02/2006; 30(11):1060-9. DOI: 10.1016/j.dci.2006.01.001
Source: PubMed


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.

Download full-text


Available from: Jack M Gallup
  • Source
    • "Constitutive expression of defensins in the sterile environments of chicken embryos (Meade et al. 2009), where many b-defensin genes were found to be differentially expressed, suggests a potential role in development. Pre-term expression of defensins has also been reported previously in sheep (Meyerholz et al. 2006). While their embryonic expression may fulfil an immunoprotective function pre-or post-natally, it is plausible, given the previously mentioned pro-angiogenic ability of defensins (Baroni et al. 2009), that defensins may also have additional roles in cell recruitment and development of the embryo. "
    [Show abstract] [Hide abstract]
    ABSTRACT: beta-defensins are effector molecules of the innate immune system, found in many diverse species. Their presence in invertebrates as well as vertebrates suggests highly conserved functional roles. Most beta-defensins are believed to act as antimicrobial agents at epithelial surfaces, although additional functions have also been described, including immune regulatory activity, wound repair and a role in coat-colour determination. High expression of beta-defensins have been found in testis and epididymidal epithelium as well as in the seminal fluid of humans, macaque, rat, mouse and cow. Human and macaque beta-defensins have recently been shown to affect sperm motility while a mutation in beta-defensin 126 is associated with reduced fertility in men. Genetic variation in bovine defensin genes may explain the increased incidence of low fertility in cattle. Here, we present a summary of the known functions of beta-defensins as well as their emerging role in reproduction and their potential to improve fertility in cattle.
    Full-text · Article · Jul 2013 · Reproduction Fertility and Development
  • Source
    • "Recent studies have demonstrated the expression of TLRs in developing embryos of different species. In sheep, TLR2 and TLR4 mRNAs increase through gestation and expression of TLR2 and TLR4 are induced by LPS treatment in the fetal sheep lung (Meyerholz et al., 2006; Hillman et al., 2008; Kramer et al., 2009). Differential expression patterns were observed in chicken in which during chick embryological development, varying expression patterns of TLR 2, TLR15 and TLR21, but not TLR4 have been reported (Meade et al., 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Toll-like receptors (TLRs) are evolutionarily conserved innate immune receptors that recognize pathogen specific molecular pattern (PAMPs) in an efficient, non-self-reactive manner and initiate specific immune signaling that culminates in triggering antigen-specific adaptive responses. Different TLR genes in domestic animal species have been characterized and accumulating evidence from recent studies indicates an extended role for TLR signaling in reproductive physiology. In females, TLRs have been implicated in the regulation of ovulation, fertilization, gestation and parturition, as well as in pathological conditions such as endometritis and mastitis. In males, TLRs play a role in steroidogenesis and spermatogenesis. Use of TLR agonists has also been shown to be effective in the treatment of certain reproductive tract infections. Moreover, gene polymorphisms in TLRs have been associated with mastitis providing evidence that TLRs can potentially be exploited as markers in future breeding programs. The aim of this review is to provide a comprehensive treatise on role of TLRs in male and female reproductive physiology and associated pathology in domestic livestock.
    Full-text · Article · May 2011 · Animal reproduction science
  • Source
    • "nous control for the genes of interest, which are listed in Table 1. We have used S15 as our endogenous control in several previous publications (Fach et al., 2007; Kawashima et al., 2006; Meyerholz et al., 2006; Sow et al., 2009) and it was previously selected after comparisons to ␤-actin and GAPDH. In addition, primers were included for a macrophage cell surface antigen, CD14, and cytokeratin 18. Cytokeratins are a subfamily of intermediate filament proteins expressed in the intracytoplasmic cytoskeleton of epithelia. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Alveolar macrophages (AMvarphis) secrete regulatory molecules that are believed to be critical in maintaining normal lung homeostasis. However, in response to activating signals, AMvarphis have been shown to become highly phagocytic cells capable of secreting significant levels of pro-inflammatory cytokines. There is evidence to suggest that susceptibility of Mvarphi subpopulations to viral infection, and their subsequent cytokine/chemokine response, is dependent on age of the host. In the present study, we compared bovine respiratory syncytial virus (BRSV) replication and induction of cytokine responses in neonatal ovine AMvarphis to those cells isolated from adult animals. While neonatal AMvarphis could be infected with BRSV, viral replication was limited as previously shown for AMvarphis from mature animals. Interestingly, following BRSV infection, peak mRNA levels of IL-1beta and IL-8 in neonatal AMvarphi were several fold higher than levels induced in adult AMvarphis. In addition, peak mRNA expression for the cytokines examined occurred at earlier time points in neonatal AMvarphis compared to adult AMvarphis. However, the data indicated that viral replication was not required for the induction of specific cytokines in either neonatal or adult AMvarphis. TLR3 and TLR4 agonists induced significantly higher levels of cytokine transcripts than BRSV in both neonatal and adult AMvarphis. It was recently proposed that immaturity of the neonatal immune system extends from production of pro-inflammatory cytokines to regulation of such responses. Differential regulation of cytokines in neonatal AMvarphis compared to adult AMvarphis in response to RSV could be a contributory factor to more severe clinical episodes seen in neonates.
    Full-text · Article · Feb 2010 · Veterinary Immunology and Immunopathology
Show more