Background

Allergic asthma is a highly heterogeneous and complex inflammatory disease of the airways, with current estimates indicating over 350 million individuals worldwide are affected (Masoli et al., 2004; Soriano et al., 2017). The classical hallmark features of the disease include elevated antigen-specific serum immunoglobulin E, CD4⁺ T-helper (Th) type 2-driven eosinophilic inflammation and reversible airways hyperresponsiveness to innocuous environmental antigens (Bousquet et al., 2000; Holgate, 2008).

Allergic asthma is recognized as a developmental disease with its inception now acknowledged to occur most commonly during the early stages of postnatal development. During this period, the inability of the functionally immature immune system to mount an efficient response to innocuous perennial aeroallergen exposure and respiratory viral infection leads to periods of exaggerated/dysregulated airways inflammation (Johnston et al., 1995; Holt et al., 2005; Jackson et al., 2016). This persistent inflammatory state within the airways can lead to loss of function and in concert with atopic sensitization during this time of immunological plasticity, promote the eventual onset of an established asthmatic phenotype during childhood (Holt et al., 2005; Jackson et al., 2016).

To elucidate the cellular and molecular mechanisms driving disease pathogenesis, murine models of experimental allergic airway disease are frequently employed (Kumar et al., 2016). It has been well established that initial sensitization at 8 weeks of age with the model antigen ovalbumin (OVA), followed by antigen challenge results in Th2-polarized airways disease, mimicking key essential clinical manifestations of human disease (von Garnier et al., 2007; Zosky et al., 2008). While 8-week-old sensitization models have provided significant advances in our understanding of asthmatic disease pathogenesis, they are not the best representative model for early life sensitization as mice attain sexual maturity at 8-12 weeks of age (Dutta and Sengupta, 2016). To address this age-dependent issue associated with murine models of allergic airway disease, this protocol sensitizes Th2-bias BALB/c mice during the early post-weanling period, paralleling that of early human childhood (Dutta and Sengupta, 2016). In brief, juvenile BALB/c mice are intraperitoneally sensitized to OVA at 21 and 35 days of age, followed by 3 consecutive OVA aerosol challenges on days 42-44 of age, with autopsy 24 h post final aerosol.