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Immune Responses to Influenza Infection in Children
Suchitra Rao1, Kent Riemondy2, Angela Dunn3
1Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA.
Insights
Influenza infection alters host gene expression in children. Vaccination helps mitigate illness severity by modulating immune responses, aligning vaccinated children
Area of Science:
- Immunology
- Genomics
- Pediatric Infectious Diseases
Background:
- Understanding host responses to severe influenza and the impact of vaccination in children is crucial.
- Current knowledge gaps exist regarding the specific pathways involved in influenza disease progression and vaccine efficacy in pediatric populations.
Purpose of the Study:
- To investigate host gene expression and cytokine profiles in children hospitalized with influenza.
- To compare these profiles between infected children and healthy controls, and between severe and non-severe cases.
- To analyze the impact of influenza vaccination on host responses and illness severity in children.
Main Methods:
- Prospective observational case-control study of children (2-18 years) with confirmed influenza.
- Comparison of blood transcriptome and plasma cytokine profiles between influenza cases and healthy controls.
- Analysis of gene expression differences based on disease severity and vaccination status.
Main Results:
- Influenza infection significantly altered gene expression in 5277 genes, primarily related to interferon and innate inflammatory responses.
- Vaccinated children showed distinct gene expression patterns, with upregulated B-cell and neutrophil responses, resembling uninfected controls.
- 102 differentially expressed genes were identified between vaccinated and unvaccinated influenza cases, indicating vaccine-induced immune modulation.
Conclusions:
- Influenza infection profoundly impacts the host transcriptome in children.
- Vaccination appears to mitigate influenza severity by altering host gene expression profiles towards a less inflammatory state.
- These findings highlight the role of host response pathways in influenza pathogenesis and vaccine effectiveness.
Background:
The host response pathways associated with progression to severe influenza disease and mechanisms of vaccination on mitigating illness severity in children are not well understood.
Methods:
We conducted a prospective observational case-control study of children aged 2 to 18 years hospitalized with polymerase chain reaction-confirmed influenza infection from 2020 to 2022. We compared the host transcriptome and cytokine profiles in blood of children within 5 days of influenza infection (cases) with healthy asymptomatic controls undergoing elective surgery. We analyzed transcription profiles as a function of (1) infected cases versus uninfected controls, (2) severe versus nonsevere, and (3) vaccinated versus unvaccinated. Pathway analysis on differentially expressed genes was performed.
Results:
Among 11 infected cases and 12 uninfected controls, there were no significant differences with respect to age, sex, or any high-risk medical condition, but a higher proportion of cases were Hispanic (45.5% vs 8.3%, P = .0007) and unvaccinated (72.7% vs 33.3%, P = .036). Compared with controls, 5277 genes were differentially expressed in influenza infection. Pathway analysis revealed major themes of gene enrichment related to interferon responses and innate inflammatory responses, confirmed with plasma cytokine analyses. We identified 102 differentially expressed genes between vaccinated and unvaccinated cases. Strong upregulation of B-cell and neutrophil responses and to a lesser extent, innate inflammatory and interferon responses, were observed in vaccinated compared with unvaccinated children. Vaccinated cases shared similar biosignatures with uninfected controls.
Conclusions:
Our study demonstrated differences in gene expression profiles of children with influenza infection that support disease mitigation through vaccination.
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