Targeting NLPR3 could lead to a turnaround

Nature: Immune cells targeting NLPR3 as a major culprit in severe COVID-19 disease may bring a turnaround

In an article published on April 28 in Nature, researchers from Yale University have identified a specific immune response that leads to severe cases of COVID-19 and even death. The study was published on Preprint platform bioRxiv on April 1.

According to a paper published in Nature on 6 April, scientists have shown that novel Coronavirus infection of monocytes causes a cytokine storm, triggering a massive inflammatory response that leads to severe respiratory distress and damage to other organs in patients with severe COVID-19 cases and is life-threatening.

In the new study, the scientists studied the immune system effects of novel coronavirus infection in a mouse model of the human immune system. In addition to lung epithelial cells, lung macrophages themselves can carry the virus, the experiments found.

Novel coronavirus replicates in macrophages

Inflammatory bodies are activated and release cytokines after novel coronavirus detection in macrophages. The inflammatory response of macrophages may be a means of blocking the replication of the Novel coronavirus, in which the infection is terminated by pyrosis (a newly discovered programmed cell death with the release of large quantities of pro-inflammatory factors). However, the cytokines released will recruit more immune cells from the blood to the lungs, exacerbating the vicious cycle of pneumonia. "It's like A broadcast system, but in this case the message is deadly," said corresponding author Richard A. Flavell.

After infection with Novel coronavirus, the inflammosome signaling pathway activates and drives macrophage pyrosis

In mouse models, the researchers prevented severe respiratory distress in mice by blocking NLPR3 inflammasome signaling. Although immune cells can still be infected by the virus, the inflammasome signaling pathway is blocked and cytokines are no longer released. Accordingly, infected immune cells do not initiate pyrophosis, viral replication restarts, and more viruses are released.

Treatment of mouse models with NLRP3 inhibitors alleviates inflammation

Nevertheless, researchers believe that blocking inflammasome signaling in combination with antiviral therapy is promising as a way to treat COVID-19 and prevent severe cases of COVID-19. No drugs that block the NLPR3 pathway are currently approved, but several companies are developing them, Flavell said.