Dissecting host immune responses to respiratory viruses in a human airway organoid-immune cell co-culture model

• Main Author: Low, Ashely Zhin Xuan
• Other Authors: Laurent Claude Stephane Renia
• Format: Final Year Project
• Language: English
• Published: Nanyang Technological University 2024
• Subjects: Medicine, Health and Life Sciences; Organoid; Co-culture; Coronavirus; Host-immune response
• Online Access: https://hdl.handle.net/10356/180996
• Institution: Nanyang Technological University

Pre-existing airway organoid models lack a comprehensive overview of host responses within infectious disease studies due to the absence of immune cells such as macrophages that contribute to innate immunity. This is a key concern as host-immune responses must be considered for a representative overview of what occurs in vivo during respiratory infections. Here, a co-culture model system involving nasopharyngeal organoids (NPOs) derived from human nasopharynx and iPSC-derived primitive macrophages (iMacs) is established to emulate host immune responses during viral infections using hCoV-NL63. NPOs were cultured on the apical chamber of transwell plates and iMacs were added at 24 hours post-infection with hCoV-NL63. Viral replication kinetics on NPOs-iMacs was investigated via vRNA extraction over 4 time points and induced innate immune responses were deduced via qPCR of pro-inflammatory cytokines and chemokines. Decreased CXCL10 gene expression was observed in the co-culture system after hCoV-NL63 infection while comparable viral replication was seen in NPOs with and without the co-culture with iMacs. These findings provided additional insight regarding the interaction between host and immune cells during human seasonal coronavirus infection. The co-culture model can be amendable to study other newly emerging respiratory viruses.