Host defense function of the airway epithelium in health and disease: clinical background

Abstract

Respiratory infection is extremely common and a major cause of morbidity and mortality worldwide. The airway epithelium has an important role in host defense against infection and this is illustrated in this review by considering infection by respiratory viruses. In patients with asthma or chronic obstructive pulmonary disease, respiratory viruses are a common trigger of exacerbations. Rhinoviruses (RV) are the most common virus type detected. Knowledge of the immunopathogenesis of such RV-induced exacerbations remains limited, but information is available from in vitro and from in vivo studies, especially of experimental infection in human volunteers. RV infects and replicates within epithelial cells (EC) of the lower respiratory tract. EC are an important component of the innate-immune response to RV infection. The interaction between virus and the intracellular signaling pathways of the host cell results in activation of potentially antiviral mechanisms, including type 1 interferons and nitric oxide, and in the production of cytokines and chemokines [interleukin (IL)-1 beta, IL-6, IL-8, IL-11, IL-16, tumor necrosis factor alpha, granulocyte macrophage-colony stimulating factor, growth-regulated oncogene-alpha, epithelial neutrophil-activating protein-78, regulated on activation, normal T expressed and secreted, eotaxin 1/2, macrophage-inflammatory protein-1 alpha], which influence the subsequent induced innate- and specific-immune response. Although this is beneficial in facilitating clearance of virus from the respiratory tract, the generation of proinflammatory mediators and the recruitment of inflammatory cells result in a degree of immunopathology and may amplify pre-existing airway inflammation. Further research will be necessary to determine whether modification of EC responses to respiratory virus infection will be of therapeutic benefit.

Figure 1

EC can be considered a component of the innate‐immune response to RV infection. Following RV infection, EC respond by the production of mediators with antiviral activity such as type 1 IFNs and nitric oxide (NO). EC production of cytokines and chemokines and the up‐regulation of major histocompatibility complex (MHC) class I and costimulatory molecules (Co stim mols) promote the recruitment of a range of inflammatory cells and through antigen presentation to lymphocytes, stimulate specific immunity. The nature of the EC response to virus infection may influence T cell/DC interaction and type 1/type 2 balance. TLRs, Toll‐like receptors.

Figure 2

Following RV infection, airway EC produce a range of cytokines and chemokines that promote recruitment and activation of inflammatory cell types including T cells, NK cells, macrophages, eosinophils, and neutrophils. Such responses facilitate clearance of virus but may amplify pre‐existing inflammation and contribute to exacerbation of diseases such as asthma and COPD. RANTES, Regulated on activation, normal T expressed and secreted; MIP‐1α, macrophage‐inflammatory protein‐1α; MCP‐1, monocyte chemoattractant protein‐1; GM‐CSF, granulocyte macrophage‐colony stimulating factor; Groα, growth‐regulated oncogene‐α; ENA78, epithelial neutrophil‐activating protein‐78.