Fig. 1

Pollen-induced activation of the innate immune system and Th2 polarization. The initiation of allergic sensitization is a complex network of diverse immune cells, such as DCs, ILC2s and neutrophils. Upon encounter with the epithelium the pollen hydrates and releases its content including allergens and various other bioactive molecules (1). At the epithelium (2), this immunogenic cocktail causes the disruption of the epithelial membrane, activates PRRs such as TLR4 and PAR2, triggers the release of alarmins (TSLP, IL-25 and IL-33), and induces oxidative stress and secretion of IL-8 and other pro-inflammatory cytokines (IL-1, IL-6 and TNFα). In turn, DCs are activated (upregulation of surface markers including OX40L and notch ligands), migrate to the lymph nodes (expression of CXCR5), where they present processed antigens via MHC-II to naïve T cells (3). Th2 polarization occurs either STAT6/GATA-3/IL-4-dependent (4A) or -independent via the NF-κB/STAT5 pathway and the contribution of ILC2s (4B). The origin of initial IL-4 for Th2 polarization is still a matter of discussion; proposed candidate are basophils and NKT cells. Once a Th2 immune response has been initiated, a class-switch of B cells to antigen-specific IgE-producing plasma cells occurs resulting in the sensitization of susceptible individuals to pollen allergens (5). CCL17, CCL22 chemokine (C–C motif) ligand 17 and 22, CCR7 C–C chemokine receptor type 7, CD80, CD86 and CD40 cluster of differentiation 80, 86 and 40, CXCL-13 C-X-C motif chemokine 13, CXCR5 C-X-C chemokine receptor type 5, DCs dendritic cells, GATA-3 GATA binding protein 3, IL- Interleukin, ILC2 type 2 innate lymphoid cells, IRF4 interferon regulatory factor 4, NF-κB nuclear factor 'kappa-light-chain-enhancer' of activated B cells, NKT natural killer T, OX40L OX40 ligand, PARs protease activated receptors, PRRs pattern recognition receptors, ROS reactive oxygen species, ST2 IL-33 receptor, STAT5, STAT6 signal transducer and activator of transcription 5 and 6, Th T helper cells, TLR4 toll-like receptor 4, TNFα Tumor necrosis factor alpha, TSLP thymic stromal lymphopoietin