Cameron Griffiths, University of Virginia

Cameron Griffiths 1; Carole Ober 2; and Peter Heymann 3,4. 1 Department of Medicine - Division of Asthma, Allergy, and Immunology, University of Virginia. 2 Department of Human Genetics, University of Chicago. 3 Child Health Research Center, University of Virginia. 4 Division of Respiratory Medicine, Allergy, Immunology, Department of Pediatrics, University of Virginia.

Expressing & Multiplying

Background: Rhinovirus (RV) infection is a key trigger of asthma exacerbations. The RV human challenge model gives insight into asthma-specific responses to RV, but has a limited range of possible experimental perturbations. In contrast, primary airway cells grown in air-liquid interface (ALI) from donors with/without asthma enable mechanistic experiments, but do not fully recapitulate the human airway. Using both model systems is ideal; however, it is unknown which human gene expression responses to RV are faithfully recapitulated by ALI cultures. Methods: Adults with/without asthma were inoculated with RV and nasal scrape samples were collected 2, 7, and 21 days after infection. Samples were analyzed by bulk RNA sequencing and compared to publicly available data of ALI cultures infected with RV for 1-4 days. Results: In a non-asthmatic setting, RV infection was associated with robust inflammation and replacement of ciliated cells by secretory cells. Furthermore, both systems displayed similar early and late responses to RV, with ALI cultures showing an accelerated infection. In contrast, humans with asthma had a blunted response to RV, which was only partially shared by asthmatic ALI cultures. Interestingly, mimicking asthmatic inflammation via paracrine co-culture of mast cells with non-asthmatic ALIs altered the response to RV, resulting in less similarity to non-asthmatic human infection. Conclusions: Non-asthmatic ALI cultures undergo an accelerated version of the human response to RV. However, asthmatic ALI cultures only partially recreate the asthma-specific response to RV. Co-culture with asthma-associated immune cells represents an intriguing path to recapitulate the asthma-specific response to RV in ALIs.