Thread by @vipintukur

#Monocytes at the Center of #SARS2 triggered inflammation & severe #Covid19

#SARS2 can cause acute respiratory distress & death in some patients. Although severe #COVID19 disease is linked to exuberant inflammation, how #SARS2 triggers inflammation is not understood. 1/

Monocytes & macrophages are the key sentinel cells that sense invasive infection to form inflammasomes that activate inflammatory cascade by secreting caspase-1 and gasdermin D, leading to inflammatory death (pyroptosis) & release of potent inflammatory mediators. 2/

~6% of monocytes in COVID patients are infected w/ SARS2

Monocyte infection depends on uptake of Ab-opsonized virus by Fcγ receptors

SARS2 begins to replicate in monocytes, but infection is aborted & infectious virus is not detected in infected monocyte culture supernatants. 3/

Instead, infected cells undergo inflammatory cell death (pyroptosis) mediated by activation of NLRP3 & AIM2 inflammasomes, caspase-1 & GSDMD

Tissue-resident macrophages, but not infected epithelial & endothelial cells, from COVID lung autopsies have activated inflammasomes. 4/

These findings suggest that antibody-mediated SARS2 uptake by monocytes/macrophages triggers inflammatory cell death that aborts production of infectious virus but causes systemic inflammation that contributes to COVID19 pathogenesis. 5/

nature.com/articles/s4158…