Differential expression of cytokine transcripts in neonatal and adult ovine alveolar macrophages in response to respiratory syncytial virus or toll-like receptor ligation

Abstract

Alveolar macrophages (AMϕs) secrete regulatory molecules that are believed to be critical in maintaining normal lung homeostasis. However, in response to activating signals, AMϕs 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 Mϕ 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 AMϕs to those cells isolated from adult animals. While neonatal AMϕs could be infected with BRSV, viral replication was limited as previously shown for AMϕs from mature animals. Interestingly, following BRSV infection, peak mRNA levels of IL-1β and IL-8 in neonatal AMϕ were several fold higher than levels induced in adult AMϕs. In addition, peak mRNA expression for the cytokines examined occurred at earlier time points in neonatal AMϕs compared to adult AMϕs. However, the data indicated that viral replication was not required for the induction of specific cytokines in either neonatal or adult AMϕs. TLR3 and TLR4 agonists induced significantly higher levels of cytokine transcripts than BRSV in both neonatal and adult AMϕs. 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 AMϕs compared to adult AMϕs in response to RSV could be a contributory factor to more severe clinical episodes seen in neonates.