Abstract
Severe viral lower respiratory infections are a major cause of infant morbidity. In developing countries, respiratory syncytial virus (RSV)-bronchiolitis induces significant mortality, whereas in developed nations the disease represents a major risk factor for subsequent asthma. Susceptibility to severe RSV-bronchiolitis is governed by gene–environmental interactions that affect the host response to RSV infection. Emerging evidence suggests that the excessive inflammatory response and ensuing immunopathology, typically as a consequence of insufficient immunoregulation, leads to long-term changes in immune cells and structural cells that render the host susceptible to subsequent environmental incursions. Thus, the initial host response to RSV may represent a tipping point in the balance between long-term respiratory health or chronic disease (e.g., asthma). The composition and diversity of the microbiota, which in humans stabilizes in the first year of life, critically affects the development and function of the immune system. Hence, perturbations to the maternal and/or infant microbiota are likely to have a profound impact on the host response to RSV and susceptibility to childhood asthma. Here, we review recent insights describing the effects of the microbiota on immune system homeostasis and respiratory disease and discuss the environmental factors that promote microbial dysbiosis in infancy. Ultimately, this knowledge will be harnessed for the prevention and treatment of severe viral bronchiolitis as a strategy to prevent the onset and development of asthma.
Highlights
Viral lower respiratory infections caused by respiratory syncytial virus (RSV) are a major cause of morbidity and mortality in young infants
Using a high-fidelity mouse model, we have demonstrated that defects in plasmacytoid dendritic cells or toll-like receptor (TLR) 7/interferon regulatory factor (IRF) 7 signaling predisposes to severe viral bronchiolitis and subsequent asthma [57,58,59,60,61]
Comparing the nasopharyngeal microbiota of these three groups, the authors found a high level of Firmicutes and the genus Streptococcus and a low level of Proteobacteria and the genera Haemophilus and Moraxella in the RSV-only group, while the opposite was true for the RV-only group and the RSV/ RV co-infection group exhibited intermediate abundances of these phyla and genera
Summary
Viral lower respiratory infections (vLRI) caused by respiratory syncytial virus (RSV) are a major cause of morbidity and mortality in young infants. Epidemiological studies have reproducibly implicated RSV-bronchiolitis as a major risk factor for the onset and progression of asthma [reviewed extensively in Ref. The Microbiome and Respiratory Disease that render the host susceptible toward allergic sensitization and asthma [2,3,4]. Susceptibility to both RSV-bronchiolitis and asthma has been attributed to defects in immunoregulatory and antiviral pathways, the cause of which may be genetic and/or environmental [1, 2, 5, 6]. Several recent studies have demonstrated changes in the respiratory microbiome in subjects with RSV-bronchiolitis [20,21,22,23]. We consider how this knowledge might be harnessed for the prevention and treatment of severe bronchiolitis as a strategy to curtail the short- and long-term burden of disease, with a specific emphasis on the onset and development of asthma
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