Differential immune responses of pediatric and adult primary epithelial cells to human respiratory pneumovirus infection 3262

Abstract Description Respiratory Syncytial Virus (RSV) and Human metapneumovirus (HMPV) are pneumoviruses causing lower respiratory tract infections, mainly in infants and children. Recently, RSV vaccines have been approved for older adults and pregnant women. However, no active immunizations against RSV or HMPV for the pediatric population exist. Therefore, a better understanding of the pediatric antiviral immune response to pneumovirus infections is warranted. Here, we assess the activation of primary human epithelial cells from children and adults infected with RSV and HMPV. We used normal human bronchial epithelial (NHBE) cells as they serve as one of the primary targets for viral replication and a source of the innate immune response to these viruses. The NHBE cells were cultured under a physiologically relevant model using an air-liquid interface (ALI) culture system. Our results indicate that pediatric and adult epithelial cells showed a differential expression of interferons, interferon-stimulated genes, inflammatory cytokines, and mucus response upon viral infection. Additional co-culture experiments with human monocyte-derived dendritic cells (mo-DCs) demonstrated that mo-DCs were differentially activated by pediatric and adult virus-infected NHBE cells. In conclusion, our findings suggest that differential immune activation between the two age groups may contribute to the age-dependent susceptibility to severe infections caused by HMPV and RSV. Funding Sources Supported by the National Institute of General Medical Sciences (5P20GM130555) from the NIH, Louisiana State University, School of Veterinary Medicine Bridge Funding Grant Topic Categories Viral Immunology (VIR)