Generation of tonsil organoids as anex vivomodel for SARS-CoV-2 infection

Abstract

SUMMARYPalatine tonsil (hereinafter referred to as “tonsil”) plays role in the immune system’s first line of defense against foreign pathogens. Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic since the infection was first reported in China in December 2019. The aim of this study was to establish tonsil epithelial cell-derived organoids and to examine their feasibility as an ex vivo model for SARS-CoV-2 infection. Using an optimized protocol, we achieved 3D tonsil organoid culture from human tonsil tissue that reflects the distinctive characteristics of the tonsil epithelium, such as its cellular composition, histologic properties, and molecular biological features. Notably, we verified that SARS-CoV-2 can infect tonsil organoids with a robust replication efficiency. Furthermore, treatment with remdesivir, an antiviral agent, effectively protected them from viral infection. Therefore, tonsil organoids could be available for investigation of SARS-CoV-2 infection-mediated pathology and for preclinical screening of novel antiviral drug candidates.One-sentence SummaryThis study established tonsil epithelial cell-derived organoids and demonstrated their feasibility as an ex vivo model for SARS-CoV-2 infection.

The SARS-CoV-2 Spike mutation D614G increases entry fitness across a range of ACE2 levels, directly outcompetes the wild type, and is preferentially incorporated into trimers

“…Sequencing analysis of human-derived tissues has identified a variety of primary cells that express the ACE2 receptors and other co-factors necessary for the infection 12,22 . Ex vivo infectivity assays have confirmed the infectibility of some of these cells by SARS-CoV-2 23–25 . The surface expression level of ACE2 on these cells varies greatly 26 .…”

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): a Systemic Infection

“…At the moment, not much data concerning the effects of SARS-CoV-2 on the immune system are available. Palatine tonsils are among the first lines of defense, and SARS-CoV-2 was reported to infect and replicate in 3D tonsil organoids, reflecting the in vivo tonsil epithelium ( 246 ). Further, other organs responsible for the immune responses were investigated, and cell degeneration or necrosis was also observed in the spleen ( 220 , 247 , 248 ).…”

Experimental Models of SARS-CoV-2 Infection: Possible Platforms to Study COVID-19 Pathogenesis and Potential Treatments

“…Cytokine/cytokine receptor interactions, apoptosis, and P53 signaling are the main cellular mechanisms activated in these organoids following SARS-CoV-2 infections (43). Since palatine tonsils are in the front line of the immune system's defense against pathogens, tonsil epithelial cell-derived organoids reflect the distinctive characteristics of the corresponding tissue and have been proposed as a platform for studying coronavirus infections and COVID-19 biology (44).…”