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.

Rhinovirus-induced lower respiratory illness is increased in asthma and related to virus load and Th1/2 cytokine and IL-10 production

“…The mechanisms by which RV infections induce lower respiratory symptoms and alterations in lung physiology in asthma are not well understood (26). However, given that primary bronchial epithelial cells from asthmatic subjects replicate RV efficiently in vitro, whereas those from normal individuals are much more resistant to Peripheral blood CD4 ϩ IFN-␥ and IL-10 production were assessed at baseline before experimental RV infection by intracellular cytokine staining.…”

Influenza A virus abrogates IFN‐γ response in respiratory epithelial cells by disruption of the Jak/Stat pathway

“…IFN-c is known to up-regulate MHC class II gene expression and regulate antigen processing by augmenting the proteolysis and peptide transport machinery in APC [13,14]. Airway epithelial cells are the initial site of respiratory virus infection and have the capacity to produce a variety of biologically active molecules, and involved in inflammation and immune responses [52]. They may act as nonprofessional APC during respiratory viral infections [9].…”

Anti-inflammatory activities ofEchinaceaextracts do not correlate with traditional marker components

“…In the case of E. purpurea, all the fractions derived from roots, leaves plus stems, and flowers, were anti-inflammatory according to IL-6 and IL-8 measurements. The cytokine IL-6 is one of the principal pro-inflammatory cytokines, and is considered to be an excellent indicator of inflammatory status (Message & Johnston, 2004;Schaller et al, 2006). The cytokine IL-8 is one of the most important chemokines which attracts neutrophils and other inflammatory cells to sites of infection (Schaller et al, 2006).…”

“…Rhinoviruses have been implicated as major players in common colds and various types of allergic rhinitis and bronchial syndromes (Message & Johnston, 2004;Schaller et al, 2006). However, numerous studies have shown that rhinovirus infection in cultured epithelial cells, and in nasal epithelial tissues in vivo, results in relatively low levels of virus replication and cytopathology, apparently due to the small number of cells supporting virus replication (Mosser et al, 2005).…”

“…However, numerous studies have shown that rhinovirus infection in cultured epithelial cells, and in nasal epithelial tissues in vivo, results in relatively low levels of virus replication and cytopathology, apparently due to the small number of cells supporting virus replication (Mosser et al, 2005). In contrast, there is substantial induction of secretion of certain pro-inflammatory cytokines and chemokines, including the important multifunctional cytokines implicated in various inflammatory conditions, interleukin-6 (IL-6) and interleukin-8, CXCL-8 (IL-8) (Message & Johnston, 2004;Sharma et al, 2006;Schaller et al, 2006;Edwards et al, 2007). Thus, the typical symptoms of a common cold, such as sneezing, coughing, runny nose, stuffed nasal passages and others are not the direct result of viral pathology, but rather the indirect stimulation of proinflammatory cytokines and chemokines.…”