Defining in vivo and in vitro models for evaluating the sensitising potential of birch pollen extracts

Various mouse models are used to study pollen allergies, but a systematic experimental comparisvon is lacking. We aimed to establish a physiologically relevant adjuvant-free birch pollen allergy model to understand the dynamics of the allergic immune response and to compare the sensitising potential of different self-collected birch pollen extracts in different distinct in vivo and in vitro routes and models.

Different intranasal (i. n.) models in BALB/c mice and IL-4 reporter mice (BALB/c:4Get), an intradermal (i. d.) model (BALB/c:4Get), and human dendritic cells (moDCs) were used to investigate the sensitising and inflammatory effects of birch pollen extracts (BPE). A timeseries experiment was performed in the i. n. model to determine the onset of Th2 responses. Bronchioalveolar lavage fluid (BALF), lungs, draining lymph nodes, and serum were analysed for cell infiltrate, cytokines, and antibodies.

Repeated i. n. instillations of adjuvant-free BPE prepared from commercial pollen resulted in BALF Th2 cells, eosinophilic lung inflammation, and specific serum immunoglobulins in BALB/c mice. After 6 i. n. instillations, eosinophils and CD4⁺ T cells peaked in BALF, and CD4⁺IL-4⁺ and CD4⁺IL4Rα⁺ cells peaked in mediastinal lymph nodes. Both, i. n. and i. d. models detected subtle differences in the sensitising potential of BPEs from two self-collected pollen samples. MoDCs showed higher IL-10 release towards the less inflammatory extract.

Adjuvant-free murine sensitisation models, including intranasal and intradermal routes, as well as a human DC model, covered different aspects of the sensitisation route and temporal resolution. The models may be broadly helpful in screening approaches in studying mechanisms of pollen allergy.