The Battle Between Influenza and the Innate Immune Response in the Human Respiratory Tract

Nicholls, John M

The mucus that is present in the airways is a mixture of cells, cellular debris and polypetpides held together by macromolecular consituents called mucins that are either in the fluid or on the surface of cells. Mucin is not a homogeneous protein but a family of glycoproteins that may either be secreted (such as MUC5AC and MUC5B) or membrane associated, that may function as cellular receptors (MUC1, MUC4, MUC11, MUC13, MUC15 and MUC20). There are a number of excellent reviews on the different types of these mucins available [28, 29] . The first set of mucins are normally secreted by goblet cells of the surface epithelium (MUC5AC and MUC5B) and submucous glands (MUC5B) present in the trachea and bronchi, and the membrane associated mucins, such as MUC1 and MUC4, are present at the apical surface of ciliated cells (Fig. 1) . The effect of mucin on influenza virus replication was initially investigated in 1942 [30] . The lectin binding studies by Baum and Paulson [22] and Lo-Guidice and colleagues [31] suggested that mucin was mainly α2-3 sialylated, and this is in keeping with mass spectrographic data that has determined the O-glycan components of mucin (Nicholls et el, unpublished results). Mucins therefore may trap avian influenza viruses because these have an affinity for α2-3 [32] . However, the successful ability of influenza to infect the respiratory epithelium is most likely due to the preference of the viral NA to cleave α2-3 linkages compared with α 2-6 linkages. Because the mucin is highly sialylated, the acidic nature of the Sia results in entrapment of water giving a viscous gel like quality to the mucin that acts as a physical barrier to infection. As children have fewer numbers of submucous glands and goblet cells than adults [33] , this reduction in number and quantity may be more susceptible to avain virus infection, such as H5N1 compared with the adult population.