Childhood respiratory viral infections and the microbiome

Abstract

The human microbiome associated with the respiratory tract is diverse, heterogeneous, and dynamic. The diversity and complexity of the microbiome and the interactions between microorganisms, host cells, and the host immune system are complex and multifactorial. Furthermore, the lymphatics provide a direct highway, the gut-lung axis, for the gut microbiome to affect outcomes related to respiratory disease and the host immune response. Viral infections in the airways can also alter the presence or absence of bacterial species, which might increase the risks for allergies and asthma. Viruses infect the airway epithelium and interact with the host to promote inflammatory responses that can trigger a wheezing illness. This immune response may alter the host's immune response to microbes and allergens, leading to T2 inflammation. However, exposure to specific bacteria may also tailor the host's response long before the virus has infected the airway. The frequency of viral infections, age at infection, sampling season, geographic location, population differences, and preexisting composition of the microbiota have all been linked to changes in microbiota diversity and stability. This review aims to evaluate the current reported evidence for microbiome interactions and the influences that viral infection may have on respiratory and gut microbiota, affecting respiratory outcomes in children.

Keywords: Asthma; T2 inflammation; asthma exacerbations; gut-lung axis; microbiome; promotion of asthma; viral infection; wheezing.

Figure 1.. T2 Immune Responses Associated with Viral Infections and the Microbiome.

Respiratory syncytial virus (RSV), rhinovirus (RV), and the bacteria Haemophilus and Moraxella have been shown to promote the production of pro-inflammatory cytokines that lead to airway hyperresponsiveness (AHR) and mucous metaplasia. (1) RSV and RV proteins are presented by Dendritic cells to naïve T cells. In the presence of IL-33, TSLP, and IL-25, these naïve T cells become T2 and release inflammatory cytokines, including IL-4, IL-5, and IL-13. T2 inflammation causes eosinophil recruitment, expansion, and activation, and B cells produce and release IgE, which binds to high affinity IgE receptor on mast cells. (2) Moraxella upregulates airway epithelial IL-33, while RSV increases IL-33 and TSLP, and RV infection increases levels of IL-25, IL-33 and TSLP. These cytokines activate group 2 innate lymphoid cells (ILC2) and Mast cells that release IL-5 and IL-13, causing AHR and eosinophil recruitment and expansion. (3) Haemophilus increases CXCL8 production, and Moraxella increases IL-8 production, suggesting that these bacteria upregulate neutrophils and cause AHR.