Tonsils may be one of the primary targets of the coronavirus. This conclusion was drawn by Korean researchers who conducted a study on organoids derived from human tonsillar epithelial cells.
How Tonsil Organoids Respond to Pathogens
After generating tonsil organoids, researchers examined how their immune response to pathogens differed from that of tonsillar tissues in patients with tonsillitis. The organoids were treated with lipopolysaccharide (LPS) to achieve this result. A molecule found in the cell walls of Gram-negative bacteria that activates innate immunity via Toll-like receptor 4 (TLR4).
Twenty-four hours post-treatment, cytokine and chemokine levels in the culture medium were measured. The tonsillar epithelium was found to produce interleukin-1 alpha (IL-1α), CXCL1, and IL-8, which attract immune cells to the inflammation site. The medium from LPS-treated organoids enhanced HL-60 cell migration—a model for immune cell movement—by 2.6-fold.
These findings confirm that tonsil organoids can respond to pathogens similarly to in vivo tonsillar tissues, releasing molecules that recruit immune cells and initiate inflammatory responses.
Can SARS-CoV-2 Infect Tonsils?
Researchers investigated whether tonsil organoids express key proteins required for coronavirus entry into cells. The ACE2 receptor, which SARS-CoV-2 binds to, was located on the outer surface of the organoids, primarily in the basal cell layer. TMPRSS2 and furin proteins, which facilitate viral entry, were uniformly distributed across the organoid surface, which indicates that tonsil organoids possess all the essential proteins necessary for SARS-CoV-2 infection, making them a viable model for studying viral infection mechanisms.
Next, researchers incubated the tonsil organoids with SARS-CoV-2 and analyzed viral protein and RNA presence two days later. Viral RNA levels increased in a dose-dependent manner, and viral particles were actively released into the surrounding environment. Electron microscopy at 72 hours post-infection confirmed the presence of numerous mature viral particles on the cell surface.
SARS-CoV-2 Suppresses Innate Immune Responses in Tonsils
Following infection, SARS-CoV-2 altered the activity of hundreds of genes, enhancing oncostatin M signaling, influencing lipid metabolism, and modulating iron transport. These changes created a favorable environment for SARS-CoV-2 replication.
At the same time, the virus suppressed 777 genes associated with innate immunity, cell growth, and brain-derived neurotrophic factor (BDNF) signaling. Reduced BDNF levels have been linked to severe COVID-19 outcomes.
These findings suggest that tonsils may serve as a reservoir for various viral infections and that SARS-CoV-2 could persist in the tonsils even after acute COVID-19 has resolved.
Conclusion
Tonsils are a critical component of the immune system, protecting the respiratory tract from infections. However, they may also function as a reservoir for viruses, including SARS-CoV-2. The study on tonsil organoids revealed that the coronavirus actively invades tonsillar epithelium and suppresses key pro-inflammatory signals, facilitating immune evasion and unrestricted viral replication.
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Reference
Generation of human tonsil epithelial organoids as an ex vivo model for SARS-CoV-2 infection
