Targeting IRF7 asthma phenotypes through immuno-modulation therapy

Viral-induced severe asthma exacerbations in children are characterized by IRF7hi and IRF7lo molecular phenotypes. We have developed an experimental animal model that mirrors these response patterns in asthma-resistant PVG and asthma-susceptible BN rats respectively. We aimed to i) characterize the immunological and molecular hallmarks of PVG and BN responses to virus/allergen exposure, and (ii) evaluate the utility of innate immune training with the bacterial lysate OM85 to attenuate ensuing inflammation. Animals were sensitized to OVA/alum, inoculated with murine-adapted Rhinovirus model (vMC0), and challenged with OVA 24h later. RNA-seq was performed on lung and bone marrow at several time points post virus/allergen exposure. 191 samples in total: 95 lung samples (48 from BN, 47 from PVG) and 96 bone marrow samples (47 from BN, 49 from PVG). Aprox half of samples are from untreated animals, the other half from OM-85 treated animals. Within each strain, tissue and treatment group, samples are further divided into four experimental groups (with n=5-7); group 1 = no OVA or virus, group 2 = no OVA with virus 1 day post infection (DPI), group 3 = OVA and virus 2 DPI, group 4 = OVA and virus 9 DPI)