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].