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Updated: Jun 22, 2025
Infection of Primary Nasal Epithelial Cells Grown at an Air-Liquid Interface to Characterize Human Coronavirus-Host Interactions
Published on: September 22, 2023
High burden of viruses and bacterial pathobionts drives heightened nasal innate immunity in children
Timothy A Watkins1,2, Alex B Green1,3, Julien A R Amat1,2
1Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA.
Insights
Children exhibit strong nasal immune responses to frequent viral and bacterial infections. These dynamic host-pathogen interactions, particularly coinfections, drive innate immune activation in the nasal passages of children.
Area of Science:
- Immunology
- Microbiology
- Pediatrics
Background:
- Children show heightened nasal innate immune responses compared to adults during the COVID-19 pandemic.
- The specific drivers of these responses, particularly the role of nasal viruses and bacteria, require further investigation.
Purpose of the Study:
- To evaluate the role of nasal viruses and bacteria in driving heightened innate immune responses in children.
- To analyze cytokine profiles and identify respiratory viruses and bacterial pathobionts in nasopharyngeal samples.
Main Methods:
- Cytokine profiling of nasopharyngeal samples from children tested for SARS-CoV-2 (2021-22).
- Comprehensive, symptom-agnostic testing for respiratory viruses and bacterial pathobionts.
- Analysis of paired samples from healthy 1-year-olds to track dynamic immune changes.
Main Results:
- High prevalence of respiratory viruses and/or pathobionts (82% symptomatic, 30% asymptomatic children).
- Virus detection and load correlated with interferon response biomarker CXCL10; viral coinfections explained SARS-CoV-2 discrepancies.
- Bacterial pathobionts correlated with distinct proinflammatory responses (IL-1β, TNF), but not CXCL10.
Conclusions:
- Frequent and dynamic host-pathogen interactions, including viral coinfections and bacterial pathobionts, are key drivers of nasal innate immune activation in children.
- Nasal immune responses are highly dynamic, changing in parallel with pathogen acquisition or clearance in young children.
Abstract:
Studies during the COVID-19 pandemic showed that children had heightened nasal innate immune responses compared with adults. To evaluate the role of nasal viruses and bacteria in driving these responses, we performed cytokine profiling and comprehensive, symptom-agnostic testing for respiratory viruses and bacterial pathobionts in nasopharyngeal samples from children tested for SARS-CoV-2 in 2021-22 (n = 467). Respiratory viruses and/or pathobionts were highly prevalent (82% of symptomatic and 30% asymptomatic children; 90 and 49% for children <5 years). Virus detection and load correlated with the nasal interferon response biomarker CXCL10, and the previously reported discrepancy between SARS-CoV-2 viral load and nasal interferon response was explained by viral coinfections. Bacterial pathobionts correlated with a distinct proinflammatory response with elevated IL-1β and TNF but not CXCL10. Furthermore, paired samples from healthy 1-year-olds collected 1-2 wk apart revealed frequent respiratory virus acquisition or clearance, with mucosal immunophenotype changing in parallel. These findings reveal that frequent, dynamic host-pathogen interactions drive nasal innate immune activation in children.
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