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Fig. 1 | Genome Medicine

Fig. 1

From: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Fig. 1

Type I IFN immunity genes associated with life-threatening COVID-19. Inborn errors of type I IFN immunity and autoantibodies neutralizing type I IFNs (α, β, ω) underlie life-threatening COVID-19 pneumonia by interfering with type I IFN immunity in respiratory epithelial cells (RECs) and blood plasmacytoid dendritic cells (pDCs). SARS-CoV-2 infection can induce type I IFN production in a TLR3-dependent manner in tissue-resident RECs (which express TLR3 but not TLR7) and in a TLR7-dependent manner in circulating pDCs (which express TLR7 but not TLR3). IRF7 is constitutively expressed in pDCs, at higher levels than in other cell types, whereas it is mostly induced by viral infection in RECs. Reported in red are the 13 genes (IFNAR1, IFNAR2, IRF3, IRF7, IRF9, IKBKG, STAT1, STAT2, TBK1, TICAM1, TLR3, TRAF3, and UNC93B1) investigated in a previous study [15]; TYK2 and TLR7 were subsequently shown to underlie severe COVID-19 [19, 30]

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Genome Medicine

ISSN: 1756-994X

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