Background Asthma is characterized by an aggravated immune response to respiratory viral infections: This phenomenon is a clinically well-recognized driver of acute exacerbations, but how different phenotypes of asthma respond immunologically to virus is unclear. Objectives To describe the association between different phenotypes and severity of asthma and bronchial epithelial immune responses to viral stimulation. Methods In the Immunoreact study, healthy subjects (n=10) and 50 patients with asthma were included; 30 (60%) were atopic, and 34 (68%) were eosinophilic; 15 (25%) had severe asthma. All participants underwent bronchoscopy with collection of bronchial brushings. Bronchial epithelial cells (BECs) were expanded and stimulated with the viral replication mimic poly (I:C) (TLR3 agonist) in vitro. The expression of TLR3-induced pro-inflammatory and anti-viral responses of BECs were analyzed using RT-qPCR and multiplex ELISA and compared across asthma phenotypes and severity of disease. Results Patients with atopic asthma had increased production of IL-4, IFN-β, IL-6, TNF-α, and IL-1β after poly (I:C) stimulation compared to non-atopic patients, whereas patients with eosinophilic asthma and non-eosinophilic asthma did not differ in the response to poly (I:C). Patients with severe asthma displayed a decreased antiviral IFN-β, and increased expression of IL-8, most pronounced in atopic and eosinophilic asthmatics. Interestingly, release of IL-33 and TSLP in response to poly (I:C) was increased in severe eosinophilic asthma, but not in severe atopic asthma. Conclusions The bronchial epithelial immune response to a viral mimic stimulation differs between asthma phenotypes and severities, which may be important to consider when targeting novel asthma treatments.