Interleukin-15 is associated with disease severity in viral bronchiolitis

Abstract

Disease severity in viral bronchiolitis in infancy is difficult to predict and has been linked to host innate immunity. The study aimed to investigate the innate cytokine interleukin-15 (IL-15) as a marker of disease severity.A prospective single-centre observational study was conducted in a university-affiliated paediatric teaching hospital, comparing children (0-18 months) hospitalised for viral bronchiolitis, those admitted to the paediatric intensive care unit with severe disease and healthy age-matched controls. IL-15-related parameters were compared between groups. PCR and microRNA (miRNA) sequencing was undertaken on natural killer (NK) cells collected from study participants.Samples from 88 children with viral bronchiolitis and 43 controls enrolled between 2009 and 2012 were analysed. Peripheral blood mononuclear cell (PBMC) IL-15 mRNA expression was significantly higher in those with moderate severity bronchiolitis compared with controls and those with severe disease. Serum IL-15 levels correlated with disease severity. The relative frequency of NK cells in peripheral blood was significantly reduced in participants with bronchiolitis. The NK cell miRNA transcriptome in bronchiolitis was distinct. Targets of de-regulated miRNA were differentially expressed in bronchiolitis, including JAK3, STAT5A and NFKB1 on the IL-15 signalling pathway.IL-15 is associated with disease severity in children hospitalised with viral bronchiolitis.@ERSpublications Interleukin-15 influences the host innate response and is associated with disease severity in viral bronchiolitis

An immune-based biomarker signature is associated with mortality in COVID-19 patients

“…In a previous study, increased serum levels of IL-15 were present in patients with early ARDS who died as compared to those who survived, whereas the opposite was true for IL-15 levels in bronchoalveolar lavage fluid (82). In another study, IL-15 serum levels correlated with disease severity in children with bronchiolitis (83). IL-15 immunotherapy, in the intent to potentiate T-and NK-cell antiviral responses, has been advocated as a potential viable strategy for COVID-19 (84); the results obtained in our study raise caution on this approach.…”

Fc-Mediated Antibody Effector Functions During Respiratory Syncytial Virus Infection and Disease

“…In mice, increased numbers of NK cells are present in the lungs early after RSV infection (43–45). In RSV-infected infants, the proportion of NK cells has been reported both to be decreased (46–49) or increased (50, 51) in comparison with healthy controls or infants with mild symptoms. Since maternally-derived antibodies are virtually always present during primary RSV infection and antibody-coated virus-infected cells are a trigger for ADCC, it can be assumed that ADCC occurs during primary RSV infection.…”

Advancing our understanding of infant bronchiolitis through phenotyping and endotyping: clinical and molecular approaches

“…Indeed, emerging evidence has shown that miRNAs participate in the maintenance of the airway epithelial barrier and are also implicated in the modulation of antiviral defense in epithelial cells. For example, Leahy et al ., by investigating miRNA expressions in NK cells in children with severe bronchiolitis and healthy controls, reported that miRNA profile is distinct in bronchiolitis and that the targets of deregulated miRNAs include NFκB on the IL-15 signaling pathway [49]. Additionally, studies using experimental models have demonstrated that respiratory viruses (e.g., RSV, rhinovirus, and influenza virus) induce distinct miRNA profiles that have different target genes and functions [48,50–54].…”