Development of Matrix-Embedded Bovine Tracheal Organoids to Study the Innate Immune Response against Bovine Respiratory Disease

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in feedlot cattle. herpesvirus-1 (BHV-1) one main culprits BRD; however, research on BHV-1 hampered by lack suitable models for infection drug testing. In this study, we established a novel bovine tracheal organoid culture grown basement membrane extract type 2 (BME2) matrix compared it with air–liquid interface (ALI) system. After differentiation, matrix-embedded organoids developed beating cilia demonstrated transcriptomic profile similar to ALI The were also highly susceptible immune stimulation Pam2Cys, an immunomodulator, which resulted robust cytokine production antimicrobial peptide mRNA upregulation. However, treatment cultures Pam2Cys was not sufficient inhibit viral or replication, suggesting role non-epithelial cellular microenvironment vivo.