Unique nasal cell states induced by common pediatric respiratory viruses

Walsh, J. M. L.; Juttukonda, L. J.; Tang, Y.; Chatterjee, A.; Elosua-Bayes, M.; Langan, E.; Frischmann, A.; Taliaferro, F.; Matthews, H. R.; Kimler, K.; Lent, C. M.; Purna Keya, D.; Chondrow Dev, P.; Rajib Malaker, A.; Tanvia, L.; Mohammad Tanmoy, A.; Ghosh, S.; Maitra, A.; Ghosh, A.; Basu, S.; Kane, A. S.; Coomer, C. A.; Shalek, A. K.; de Silva, T. I.; Sesay, A. K.; Edwards, J.; Sin Quee, C.; Gonzalez, W. I.; Yonker, L. M.; Glover, S. C.; Majumder, P.; Hooda, Y.; Saha, S.; Ordovas-Montanes, J.; Horwitz, B. H.

doi:10.64898/2026.04.20.719671

Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.04.20.719671

Unique nasal cell states induced by common pediatric respiratory viruses

View original source ↗Export metadata ↓

Abstract

Respiratory viral infections in early childhood are major drivers of acute morbidity and long-term airway disease, yet how distinct viruses remodel the pediatric nasal mucosa at cellular resolution remains unresolved. Here, we generated a single-cell RNA sequencing atlas of 335,174 nasal epithelial and immune cells from 132 children under five years of age with SARS-CoV-2, rhinovirus, or respiratory syncytial virus (RSV) infection, alongside uninfected controls. Mapping viral transcripts to individual cells revealed virus-specific infected epithelial states: an NF-kB-responsive ciliated subset in SARS-CoV-2 and a previously undescribed KRT17+ squamous-like subset in RSV. We delineated divergent mucosal response programs, including a robust interferon (IFN) response in SARS-CoV-2, an IL-13-responsive secretory program in rhinovirus, and heightened inflammatory and cytotoxic immune activation in RSV. In RSV, specific immune subsets and elevated IFN-response signatures were associated with disease severity, whereas rhinovirus-induced wheeze was marked by expansion of a CST1+ goblet cell subset. Integration of asthma genome-wide association data with our atlas revealed a KRT13+ hillock-like squamous epithelial subset enriched for expression of childhood-onset asthma risk loci. Finally, we demonstrate that this resource enables high-resolution annotation of independent pediatric cohorts in Kolkata, India and rural Bangladesh. Together, this atlas establishes a comprehensive view of antiviral immunity in the pediatric nasal mucosa and defines virus-specific mucosal immune programs relevant to disease severity and asthma risk in early life.

Explore related subjects

immunology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Walsh, J. M. L., Juttukonda, L. J., Tang, Y., Chatterjee, A., Elosua-Bayes, M., Langan, E., Frischmann, A., Taliaferro, F., Matthews, H. R., Kimler, K., Lent, C. M., Purna Keya, D., Chondrow Dev, P., Rajib Malaker, A., Tanvia, L., Mohammad Tanmoy, A., Ghosh, S., Maitra, A., Ghosh, A., Basu, S., Kane, A. S., Coomer, C. A., Shalek, A. K., de Silva, T. I., Sesay, A. K., Edwards, J., Sin Quee, C., Gonzalez, W. I., Yonker, L. M., Glover, S. C., Majumder, P., Hooda, Y., Saha, S., Ordovas-Montanes, J., Horwitz, B. H.. 2026-04-22. Unique nasal cell states induced by common pediatric respiratory viruses. https://doi.org/10.64898/2026.04.20.719671

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Common viral infections seed regionally distinct resident memory T cells in the human CNS

T cells persist in the central nervous system (CNS) and can drive both protection and neurological disease. How these cells are organized in humans and what they recognize is largely unknown. Here, we profiled CD8 T cells across anatomically distinct CNS regions, obtained through on-site autopsies and temporal lobe resection surgeries, using single-cell RNA sequencing, paired T cell receptor sequencing, and DNA-barcoded tetramers. Resident memory T cells (TRM) specific for Epstein-Barr virus, cytomegalovirus, influenza A, and SARS-CoV-2 were identified across CNS compartments. Anatomical location was the strongest correlate of TRM cell state, with leptomeningeal cells adopting a cytokine-poised TRM program, whereas brain TRM cells were transcriptionally restrained. Cells of the same clonotype spanned tissues yet adopted local transcriptional states. Viral specificity added another layer of TRM heterogeneity with GZMK/GZMA-expressing EBV-specific populations and interferon-stimulated gene signatures in SARS-CoV-2 and Influenza A-specific cells. The human CNS thus harbors regionally distinct CD8+ TRM shaped by common viral exposures.

immunology↗

bioRxiv2026

A regulatory T cell signature provides a shared molecular basis for the therapeutic window of opportunity in rheumatic disease

Rheumatic diseases, including rheumatoid arthritis (RA), spondyloarthritis (SpA) and osteoarthritis (OA), show distinct phenotypes yet respond to overlapping therapies, implicating shared immune mechanisms. In the Transimmunom cohort, we profiled peripheral blood from 240 individuals (47 healthy, 44 OA, 91 RA, 58 SpA) across deep immunophenotyping, immunoproteomics and Treg-Teff transcriptomics. Single-layer analyses revealed broader Treg than Teff remodeling, along with a shared pattern of reduced activated Tregs and expanded Helios+ Tregs across all diseases, alongside a decrease in functional Treg subpopulations, including CTLA4+ and CD45RA- Tregs. In RA specifically, LAG3+ Tregs were also expanded. Combining omics layers outperformed single-layer approaches for disease classification. Among individual layers, Treg transcriptomes were most discriminative, and integration uncovered disease-specific programs. Unsupervised clustering identified a cross-disease cluster independent of activity, treatment and age, mapping to early disease (<= years) and dominated by a Treg dysfunction-associated program. These results provide a biological rationale for the therapeutic "window of opportunity" concept and duration-stratified Treg-directed trials.

immunology↗

bioRxiv2026

Inhibitory Fc Receptor sets a time limit on macrophage response to IgG

Antibodies engage both activating Fc Receptors and the inhibitory receptor Fc{gamma}RIIB. Why macrophages need a dedicated inhibitory receptor rather than simply tuning activating receptor signaling is unclear. Using DNA-based chimeric receptors and in silico modeling, we independently controlled activating and inhibitory Fc Receptors. We found that Fc{gamma}RIIB imposed a time limit on macrophage phagocytosis and ERK signaling. The time limit is due to activating Fc Receptors converting PI(4,5)P2 to PI(3,4,5)P3, which is subsequently converted to PI(3,4)P2 by Fc{gamma}RIIB. This leads to a pulse of active signaling, which is sufficient for phagocytosis of small bacteria-sized targets but not phagocytosis of large targets and TNF secretion. Unlike engaging Fc{gamma}RIIB, reducing activating Fc Receptor signaling decreased initiation of phagocytosis, the speed of PI(3,4,5)P3 generation, and the amplitude of ERK signaling. Our results demonstrate that Fc{gamma}RIIB controls the duration of IgG signaling, while the activating Fc Receptors control sensitivity.

immunology↗