3.1 Thymic Stromal Lymphopoietin (TSLP)
Clinical and experimental studies showed that TSLP, a cytokine primarily expressed by epithelial cells, is induced by RSV infections [39,40]. Evaluating infants hospitalized with bronchiolitis (70% due to RSV), and matched healthy infants at their primary care appointments, García-García et al showed upregulation of TSLP levels in nasopharyngeal aspirates of the bronchiolitis group [41]. Among RSV-infected infants, those who needed ICU admission presented more frequently detectable and higher TSLP concentrations. Moreover, when primary BEC cultures obtained by cytologic brushings from children were exposed to RSV, a rapid and significantly higher TSLP production was detected in asthmatics, as compared to healthy control [42]. In wild-type mice, TSLP levels were increased 12 hours after infection and significant increase in IL-13–producing ILC2 and in lung IL-13 levels was observed on day 4 after infection [43]. TSLPR knockout (KO) mice did not mount an IL-13–producing ILC2 response to RSV infection, displayed reduced lung IL-13 protein levels, decreased airway mucus and hyperreactivity, as compare with wild-type mice [43]. Gender differences may also impact on TSLP-induced immune alterations following early-life RSV infection [44]. As compared to neonatal female mice, neonatal male mice infected with RSV exhibited higher viral loads and lower IFNβ production and delayed infection resolution, on day 4 post-infection. At 4 weeks post-infection, neonatal male but not female mice, had higher TSLP and IL-33 levels in their lungs, increased IL-13 gene expression in lung ILC2, airway reactivity and mucus secretion [44]. These changes in male mice were associated with an increased susceptibility to allergic exacerbation upon allergen challenge at 4 weeks of age [44].