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Updated: Jul 1, 2025
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
Differential anti-viral response to respiratory syncytial virus A in preterm and term infants
Jeremy Anderson1, Samira Imran1, Yan Yung Ng1
1Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia.
Insights
Preterm infants show a limited immune response to respiratory syncytial virus (RSV) A compared to term infants. This restricted response may explain their higher susceptibility to severe RSV disease.
Area of Science:
- Immunology
- Neonatal Research
- Virology
Background:
- Preterm infants are at higher risk for severe respiratory syncytial virus (RSV) disease.
- Immature immune systems are a key factor in preterm infants' vulnerability to RSV.
Purpose of the Study:
- To compare the immune response to RSV in preterm and term infants.
- To identify immunological differences that may explain increased RSV severity in preterm infants.
Main Methods:
- Cord blood mononuclear cells (CBMCs) from 25 preterm and 25 term infants were stimulated with RSV A (RSVA) and RSV B (RSVB).
- Analyses included neutralising assays, high-dimensional flow cytometry, multiplex cytokine assays, and RNA-sequencing.
- Differential gene expression was analyzed to compare immune responses.
Main Results:
- Maternal antibody titers to RSVA and RSVB were similar in both groups.
- Preterm infants exhibited higher myeloid dendritic cell (mDC) infection rates with RSV.
- RSVA stimulation in term infants activated cytokine production and immune regulatory pathways, unlike in preterm infants, whose responses were linked to cell cycle genes.
Conclusions:
- Preterm infants demonstrate a more restricted immunological response to RSVA compared to term infants.
- These findings suggest a potential explanation for increased RSV severity in preterm infants.
- The study identifies potential therapeutic targets for protecting vulnerable preterm infants from RSV.
Background:
Preterm infants are more likely to experience severe respiratory syncytial virus (RSV) disease compared to term infants. The reasons for this are multi-factorial, however their immature immune system is believed to be a major contributing factor.
Methods:
We collected cord blood from 25 preterm (gestational age 30.4-34.1 weeks) and 25 term infants (gestation age 37-40 weeks) and compared the response of cord blood mononuclear cells (CBMCs) to RSVA and RSVB stimulation using neutralising assays, high-dimensional flow cytometry, multiplex cytokine assays and RNA-sequencing.
Findings:
We found that preterm and term infants had similar maternally derived neutralising antibody titres to RSVA and RSVB. Preterm infants had significantly higher myeloid dendritic cells (mDC) RSV infection compared to term infants. Differential gene expression analysis of RSVA stimulated CBMCs revealed enrichment of genes involved in cytokine production and immune regulatory pathways involving IL-10, IL-36γ, CXCL1, CXCL2, SOCS1 and SOCS3 in term infants, while differentially expressed genes (DEGs) in preterm infants were related to cell cycle (CDK1, TTK, ESCO2, KNL1, CDC25A, MAD2L1) without associated expression of immune response genes. Furthermore, enriched genes in term infants were highly correlated suggesting an increased co-ordination of their immune response to RSVA. When comparing DEGs in preterm and term infants following RSVB stimulation, no differences in immune response genes were identified.
Interpretation:
Overall, our data suggests that preterm infants have a more restricted immunological response to RSVA compared with term infants. While further studies are required, these findings may help to explain why preterm infants are more susceptible to severe RSV disease and identify potential therapeutic targets to protect these vulnerable infants.
Funding:
Murdoch Children's Research Institute Infection and Immunity theme grant.
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