Upper respiratory tract epithelial cells exhibited similar inflammatory signaling responses across respiratory viral infections, while influenza A-infected cells from younger children showed heightened interferon signaling compared with those from older children, according to findings presented at IDWeek 2026.
Although children are disproportionately affected by influenza and other respiratory viruses that infect upper respiratory tract epithelial cells and initiate host defense responses, how these cells respond to infection remains poorly understood. Presenting author Emily Parsons, MD, PhD, a researcher at the Laboratory of Infectious Diseases and Host Defense at Uniformed Services University in Bethesda, Maryland, and colleagues sought to characterize the epithelial cell types infected by respiratory viruses and their signaling profiles.
The investigators analyzed upper respiratory tract cells isolated from nasopharyngeal samples collected from children aged 1 month to 17 years enrolled in the Pediatric Respiratory Co-infection and Immunologic Response Study. Samples were obtained at healthy baseline (n = 47) and during acute respiratory infection (n = 27). Cellular transcriptomic profiles were analyzed using single-cell RNA sequencing, and pseudoalignment with kallisto was performed to identify intracellular viral transcripts.
The analysis identified eight epithelial cell types: ciliated, club, FOXN4-positive, ionocyte, basal, goblet, differentiating secretory and squamous cells.
During acute infection, investigators identified an inflammatory subcluster across epithelial cell types characterized by enriched Toll-like receptor 3 and interferon signaling. Subclustering of ciliated epithelial cells, for example, revealed an inflammatory cluster with upregulated interferon-alpha, interferon-beta and interferon-gamma signaling, as well as Toll-like receptor 3 and cell death pathways.
Among participants with polymerase chain reaction-confirmed viral infections, viral transcripts were detected within inflammatory cell clusters. Similar inflammatory transcriptomic profiles were observed during acute infection regardless of the specific viral pathogen.
“Interestingly, the majority of epithelial subsets were infected with influenza, as determined by the presence of viral transcripts, although with differing frequencies,” the authors wrote.
Influenza-infected epithelial cells from younger children aged 0 to 5 years exhibited higher type I and type II interferon signaling than those from older children aged 6 to 18 years.
“Our study characterized distinct epithelial subsets in the upper airway of children acutely infected with influenza and other respiratory viruses,” the authors concluded. “Our study highlights common signaling cascade activation in respiratory epithelial cells among respiratory viruses and heightened [interferon] signaling in younger children in response to influenza.”
Of the authors who provided disclosure information, none reported conflicts of interest.