3. ALARMINS, ILC ACTIVATION IN RSV INFECTION AND WHEEZING/ASTHMA
In response to RSV, other viruses as well as allergens and other triggers involved in wheezing/asthma pathogenesis, airway epithelium can directly stimulate ILC2 to release IL-4, IL-5, and IL-13 through the release of alarmins (figure 2). IL-4 drives Th2 cell differentiation and promotes B cell antibody class switch to IgE-producing-plasma cells [31-33]. IL-5 recruits and enhances survival of eosinophils, major component of the Th2 inflammatory infiltrates [34,35]. IL-13 increases goblet cell mucin expression and development of airway hyperresponsiveness [36]. Thus, the alarmins IL-33, IL-25, TSLP and HMGB1, through ILC2 activation, can play a significant role in promoting the progression of Th2 type response in infants with RSV bronchiolitis and in increasing the risk of developing recurrent wheezing/asthma and, possibly, susceptibility to allergic exacerbation in later life [37].