Airway mir-155 responses are associated with TH1 cytokine polarization in young children with viral respiratory infections

• Published in: PloS one Vol. 15; no. 5; p. e0233352
• Main Authors: Arroyo, Maria, Salka, Kyle, Chorvinsky, Elizabeth, Xuchen, Xilei, Abutaleb, Karima, Perez, Geovanny F, Weinstock, Jered, Gaviria, Susana, Gutierrez, Maria J, Nino, Gustavo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.05.2020; Public Library of Science (PLoS)
• Subjects: Airway; Antiviral agents; Antiviral drugs; Biochemistry; Biology and Life Sciences; Child health; Children; Cytokines; Cytokines - genetics; Cytokines - metabolism; Diseases; Female; Gene expression; Genes; Genetic aspects; Health aspects; Humans; Hypersensitivity; IL-1β; Immune system; Immunity; Infant; Infants; Infection; Infections; Inflammation; Interleukin 13; Interleukin 4; Lung diseases; Lymphocytes T; Male; Medicine and Health Sciences; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; NF-κB protein; Pediatric research; People and Places; Physiological aspects; Polarization; Respiratory diseases; Respiratory syncytial virus; Respiratory Syncytial Virus Infections - genetics; Respiratory Syncytial Virus Infections - metabolism; Respiratory Syncytial Virus Infections - virology; Respiratory Syncytial Viruses - isolation & purification; Respiratory System - metabolism; Respiratory System - virology; Respiratory tract; Respiratory tract diseases; Respiratory tract infection; Respiratory tract infections; Respiratory Tract Infections - genetics; Respiratory Tract Infections - metabolism; Respiratory Tract Infections - virology; Rhinovirus; Rhinovirus - isolation & purification; T cells; Tumor necrosis factor-α; Viral infections; Virus diseases; Viruses; γ-Interferon; United States; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0233352

MicroRNAs (miRs) control gene expression and the development of the immune system and antiviral responses. MiR-155 is an evolutionarily-conserved molecule consistently induced during viral infections in different cell systems. Notably, there is still an unresolved paradox for the role of miR-155 during viral respiratory infections. Despite being essential for host antiviral TH1 immunity, miR-155 may also contribute to respiratory disease by enhancing allergic TH2 responses and NFkB-mediated inflammation. The central goal of this study was to define how airway miR-155 production is related to TH1, TH2, and pro-inflammatory cytokine responses during naturally occurring viral respiratory infections in young children. Normalized nasal airway levels of miR-155 and nasal protein levels of IFN-γ, TNF-α, IL-1β, IL-13, IL-4 were quantified in young children (≤2 years) hospitalized with viral respiratory infections and uninfected controls. These data were linked to individual characteristics and respiratory disease parameters. A total of 151 subjects were included. Increased miR-155 levels were observed in nasal samples from patients with rhinovirus, RSV and all respiratory viruses analyzed. High miR-155 levels were strongly associated with high IFN-γ production, increased airway TH1 cytokine polarization (IFN-γ/IL-4 ratios) and increased pro-inflammatory responses. High airway miR-155 levels were linked to decreased respiratory disease severity in individuals with high airway TH1 antiviral responses. The airway secretion of miR-155 during viral respiratory infections in young children is associated with enhanced antiviral immunity (TH1 polarization). Further studies are needed to define additional physiological roles of miR-155 in the respiratory tract of human infants and young children during health and disease.