Neonatal immune response to rhinovirus A16 has diminished dendritic cell function and increased B cell activation

Abstract

Background: Rhinovirus infections during infancy account for the majority of respiratory illness health care utilization and are an associated risk factor for subsequent development of allergic asthma. Neonatal type I interferon production is diminished compared to adults after stimulation with TLR agonists. However, broad profiling of immune cell responses to infectious rhinovirus has not been undertaken and we hypothesized that additional immune differences can be identified in neonates. In this study, we undertook a comparative analysis of neonatal and adult blood immune cell responses after in vitro incubation with infectious RV-A16 for 6 and 24 hours. Methods: Intracellular proinflammatory and type I interferon cytokines along with expression of surface co-stimulatory and maturation markers were measured using multi-parameter flow cytometry. Results: Both circulating myeloid dendritic cell (mDC) and plasmacytoid dendritic cell (pDC) frequency were lower in cord blood. Qualitative and quantitative plasmacytoid dendritic cell IFN-alpha + TNF- alpha responses to rhinovirus were significantly lower in cord pDCs. In cord blood samples, the majority of responsive pDCs were single-positive TNF-alpha producing cells, whereas in adult samples rhinovirus increased double-positive TNF-alpha +IFN-alpha+ pDCs. Rhinovirus upregulated activation and maturation markers on monocytes, mDCs, pDCs, and B cells, but CD40+CD86+ monocytes, mDCs, and pDCs cells were significantly higher in adult samples compared to cord samples. Surprisingly, rhinovirus increased CD40+CD86+ B cells to a significantly greater extent in cord samples compared to adults. Conclusions: These findings define a number of cell-specific differences in neonatal responses to rhinovirus. This differential age-related immune response to RV may have implications for the immune correlates of protection to viral respiratory illness burden and determination of potential biomarkers for asthma risk.