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.
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.
Meyerholz
David K
DK
Department of Veterinary Pathology, 2740 College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA. dmeyerho@iastate.edu
Kawashima
Kenji
K
Gallup
Jack M
JM
Grubor
Branka
B
Ackermann
Mark R
MR
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000276:immunology*; D011247:Pregnancy; D037662:Pulmonary Surfactant-Associated Protein A / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep / Q000235:genetics* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D023083:beta-Defensins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
C406407:DEFB1 protein, human; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D051197:Toll-Like Receptor 4; D023083:beta-Defensins