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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
Bacterial small RNAs may mediate immune response differences seen in respiratory syncytial virus versus rhinovirus
Kylie I Krohmaly1,2, Marcos Perez-Losada3, Ignacio Ramos-Tapia4
1Integrated Biomedical Sciences, The George Washington University, Washington, DC, United States.
Insights
Bacterial small RNAs (sRNAs) differ between respiratory syncytial virus (RSV) and rhinovirus (RV) bronchiolitis in infants. These sRNAs may influence inflammatory pathways, potentially explaining differences in infant immune responses to RSV versus RV infections.
Area of Science:
- Microbiology and Immunology
- Pediatric Respiratory Medicine
- RNA Biology
Background:
- Bronchiolitis, a common infant respiratory infection, is linked to later asthma development.
- Respiratory syncytial virus (RSV) and rhinovirus (RV) are primary causes of bronchiolitis, with distinct immune responses observed.
- Bacterial small RNAs (sRNAs), analogous to human microRNAs, are increasingly recognized for their role in inter-species communication and host modulation.
Purpose of the Study:
- To identify and compare bacterial sRNAs present in infants with RSV-only versus RV-only bronchiolitis.
- To investigate the potential impact of these bacterial sRNAs on host inflammatory pathways.
- To explore the role of bacterial sRNAs in mediating differential immune responses observed in RSV vs. RV bronchiolitis.
Main Methods:
- Development of reference sRNA datasets from four key bacteria associated with bronchiolitis: *Haemophilus influenzae*, *Moraxella catarrhalis*, *Moraxella nonliquefaciens*, and *Streptococcus pneumoniae*.
- Analysis of human nasal RNA-Seq data from the MARC-35 cohort to identify bacterial sRNAs associated with RSV-only and RV-only bronchiolitis.
- Bioinformatic prediction of human mRNA targets for identified bacterial sRNAs and comparison of sRNA expression profiles between RSV and RV cases.
Main Results:
- Several bacterial sRNAs were identified and associated with either RSV-only or RV-only bronchiolitis.
- Bacterial sRNAs linked to RSV-only bronchiolitis showed potential to activate IL-6 and IL-8 pathways.
- Compared to RV-only bronchiolitis, RSV-associated bacterial sRNAs may relatively inhibit the IL-17A pathway.
Conclusions:
- Bacterial sRNAs represent a novel mechanism contributing to differential inflammatory responses in infants with RSV versus RV bronchiolitis.
- These findings highlight the complex interplay between viral infections, bacterial communities, and host immunity in early life respiratory diseases.
- Targeting bacterial sRNAs could offer new therapeutic strategies for managing bronchiolitis and potentially mitigating long-term asthma risk.
Abstract:
Bronchiolitis, a viral lower respiratory infection, is the leading cause of infant hospitalization, which is associated with an increased risk for developing asthma later in life. Bronchiolitis can be caused by several respiratory viruses, such as respiratory syncytial virus (RSV), rhinovirus (RV), and others. It can also be caused by a solo infection (e.g., RSV- or RV-only bronchiolitis) or co-infection with two or more viruses. Studies have shown viral etiology-related differences between RSV- and RV-only bronchiolitis in the immune response, human microRNA (miRNA) profiles, and dominance of certain airway microbiome constituents. Here, we identified bacterial small RNAs (sRNAs), the prokaryotic equivalent to eukaryotic miRNAs, that differ between infants of the 35th Multicenter Airway Research Collaboration (MARC-35) cohort with RSV- versus RV-only bronchiolitis. We first derived reference sRNA datasets from cultures of four bacteria known to be associated with bronchiolitis (i.e., Haemophilus influenzae, Moraxella catarrhalis, Moraxella nonliquefaciens, and Streptococcus pneumoniae). Using these reference sRNA datasets, we found several sRNAs associated with RSV- and RV-only bronchiolitis in our human nasal RNA-Seq MARC-35 data. We also determined potential human transcript targets of the bacterial sRNAs and compared expression of the sRNAs between RSV- and RV-only cases. sRNAs are known to downregulate their mRNA target, we found that, compared to those associated with RV-only bronchiolitis, sRNAs associated with RSV-only bronchiolitis may relatively activate the IL-6 and IL-8 pathways and relatively inhibit the IL-17A pathway. These data support that bacteria may be contributing to inflammation differences seen in RSV- and RV-only bronchiolitis, and for the first time indicate that the potential mechanism in doing so may be through bacterial sRNAs.
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