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Recent research indicates that exposure to pollen increases the risk and severity of respiratory infections, while studies also suggest that it may possess a protective function. Our aim was to investigate how exposure to common pollen modifies airway cells’ responses to viral- or bacterial-like challenges and vice versa. Cocultured A549 and THP-1 cells were exposed to three doses of four different pollens (Alnus glutinosa, Betula pendula, Phleum pratense, or Ambrosia artemisiifolia) and subsequently to Toll-like receptor (TLR) ligands mimicking bacterial and viral challenges (TLR3, TLR4, TLR7/8). The stimulation experiment was replicated in reverse order. Toxicological and immunological end points were analyzed. When cells were primed with pollen, especially with grass (P. pratense) or weed (A. artemisiifolia), the ability of cells to secrete cytokines in response to bacterial- and viral-like exposure was decreased. In contrast, cells primed with viral ligand TLR7/8 showed greater cytokine responses against pollen than cells exposed to ligands or pollen alone. Our results suggest that pollen exposure potentially weakens immune reactions to bacterial- or viral-like challenges by modulating cytokine production. They also indicate that TLR7/8-mediated viral challenges could elicit exaggerated immune responses against pollen. Both mechanisms could contribute to the acceleration and complication of infections during the pollen season.