Neonatal alveolar macrophages upregulate cytokine gene transcription via p38 MAPK signaling but fail to secrete cytokines in response to Respiratory Syncytial Virus

Abstract

<p>Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis and pneumonia in premature and newborn infants. We examined the role of alveolar macrophages (AMs) in a model of RSV infection. Additionally, the contribution of MAPK signaling to cytokine expression was delineated via p38 inhibitor SB203580. AMs isolated from neonatal and adult sheep were infected with BRSV in vitro with or without SB203580 pre-treatment. Expression of cytokine mRNA and protein secretion was determined. Results showed that RSV infection induced IL-1b, IL-4, IL-6, IL-8, and IL-10 gene expression. Furthermore, RSV induction of IL-6, IL-8 and IL-1b mRNA in neonatal and adult AMs, as well as IL-10 protein from adult AMs, was p38 MAPK-dependent. Significantly higher IL-1b mRNA was detected in RSV-infected neonatal AMs than adult cells. Paradoxically, neonatal AMs did not secrete IL-1b, IL-4, or IL-10. Inhibition of cytokine secretion by RSV may contribute to the increased susceptibility and severity of disease in neonates.</p>