Studies have revealed that infected immune cells prompt a massive inflammatory response.
, Judy Lieberman, an immunologist at the Boston Children’s Hospital in Massachusetts, and her colleagues looked at blood samples from people with COVID-19. They found that about 6% of monocytes — ‘early responder’ immune cells that patrol the body for foreign invaders — were undergoing a type of cell death associated with inflammation, known as pyroptosis. To see that many cells dying is unusual, she says, because the body typically gets rid of dead cells quickly.
The researchers also looked at another type of immune cell, macrophages, in the lungs of people who had died of COVID-19. Because macrophages collect cellular garbage, including viral debris, it has been difficult to show whether macrophages were infected with SARS-CoV-2 or just sopping up this debris. The team found that about a quarter of macrophages had activated inflammasomes, and a fraction of those had indeed been infected with the virus.
The macrophages’ inflammatory response could be their way of stopping SARS-CoV-2 from replicating, says study co-author Richard Flavell, an immunologist, also at Yale, and the Howard Hughes Medical Institute. When inflammasomes were activated, the virus stopped replicating in the cells. But when the researchers blocked inflammasomes, the macrophages started producing infectious virus particles.
Lieberman says this is also how the virus enters monocytes, which do not have ACE2 receptors. Only monocytes with the Fcγ receptor could be infected.