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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Infant-derived human nasal organoids exhibit relatively increased susceptibility, epithelial responses, and
Gina M Aloisio1, Divya Nagaraj2, Ashley M Murray2
1Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Insights
Infant nasal epithelium shows greater susceptibility to respiratory syncytial virus (RSV) replication and a more severe inflammatory response compared to adults. These differences in the upper respiratory tract contribute to more severe RSV infections in children.
Area of Science:
- Pediatric infectious diseases
- Respiratory virology
- Epithelial biology
Background:
- Respiratory syncytial virus (RSV) causes significant illness in young children.
- The reasons for increased RSV severity in children versus adults are not fully understood.
Purpose of the Study:
- To investigate the cellular mechanisms underlying RSV severity disparities between infants and adults.
- To compare the response of infant and adult nasal epithelium to RSV infection.
Main Methods:
- Utilized ex-vivo human nasal organoid-air liquid interface (HNO-ALI) platforms derived from infants and adults.
- Assessed early RSV replication, cytokine production, mucous secretion, and cellular damage in HNO-ALIs.
Main Results:
- Infant-derived HNO-ALIs exhibited higher susceptibility to early RSV replication.
- Infant HNO-ALIs showed significantly greater cytokine response, increased mucous production, and more cellular damage.
- Adult HNO-ALIs demonstrated a superior regulatory cytokine response, correlating with less cellular damage.
Conclusions:
- Significant differences exist in infant versus adult upper respiratory tract epithelial responses to RSV.
- Impaired mucociliary clearance and dysregulated innate immunity in infants contribute to more severe RSV infections.
- These findings provide cellular-level insights into pediatric RSV disease severity.
Background:
Respiratory syncytial virus (RSV) causes significant morbidity and mortality, especially in young children. Why RSV infection in children is more severe compared to healthy adults is not fully understood.
Methods:
We used ex-vivo human nasal organoid platforms from infants and adults to investigate the underlying mechanism of this disease disparity at the initial site of RSV replication, the nasal epithelium.
Results:
Infant-derived human nasal organoid-air liquid interface (HNO-ALIs) lines were more susceptible to early RSV replication. Moreover, infant-derived HNO-ALIs elicited a statistically significant greater overall cytokine response, enhanced mucous production, and greater cellular damage compared to their adult counterparts. Furthermore, the adult cytokine response was associated with a superior regulatory cytokine response, which could explain less cellular damage than in infant lines.
Conclusions:
Our data highlights substantial differences in how infant and adult upper respiratory tract epithelium responds to RSV infection at the cellular level. These differences in epithelial cellular response can lead to impaired mucociliary clearance, a more dysregulated innate immune response predisposing infants to more severe RSV infection compared to adults.
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