Bacterial small RNAs may mediate immune response differences seen in respiratory syncytial virus versus rhinovirus bronchiolitis

Kylie I. Krohmaly, Integrated Biomedical Sciences, The George Washington University, Washington, DC, United States.
Marcos Perez-Losada, Department of Biostatistics and Bioinformatics, Computational Biology Institute, The George Washington University, Washington, DC, United States.
Ignacio Ramos-Tapia, Centro de Bioinformática y Biología Integrativa, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, Chile.
Zhaozhong Zhu, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Kohei Hasegawa, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Carlos A. Camargo, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Brennan Harmon, Center for Genetic Medicine Research, Children's National Research and Innovation Center, Washington, DC, United States.
Janice A. Espinola, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Laura Reck Cechinel, Center for Genetic Medicine Research, Children's National Research and Innovation Center, Washington, DC, United States.
Rachael Batabyal, Center for Genetic Medicine Research, Children's National Research and Innovation Center, Washington, DC, United States.
Robert J. Freishtat, Center for Genetic Medicine Research, Children's National Research and Innovation Center, Washington, DC, United States.
Andrea Hahn, Center for Genetic Medicine Research, Children's National Research and Innovation Center, Washington, DC, United States.

Document Type

Journal Article

Publication Date

1-1-2024

Journal

Frontiers in immunology

Volume

15

DOI

10.3389/fimmu.2024.1330991

Keywords

Haemophilus influenzae; RNA; Streptococcus pneumoniae; bronchiolitis; extra cellular vesicles; respiratory syncytial virus; rhinovirus

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 35 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., , , , and ). 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.

Department

Pediatrics

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