Studies in humans and mice reveal a critical role for CCR2 in trafficking of pDCs during infection with SARS-CoV-2

Abstract Although GWAS have implicated chemokine receptors in affecting disease severity, the role of chemokines COVID-19 pathogenesis has not been defined. To bridge this gap, we surveyed expression 14 on blood leukocytes from 19 hospitalized patients vs. healthy controls. Among many differences between and controls, found that CCR2, which shown mediates lymphocyte transendothelial migration, was down patient MAIT cells pDCs, whose numbers are depressed COVID-19. If a receptor extravasation, lower levels could result efficient, thereby preferential migration expressing higher into infected tissue. In support mechanism, enrichment CCR2 highcells among migrating to ligand, CCL2, vitro. test if leukocyte extravasation transgenic K18-hACE2 Ccr2 reporter mice were +/RFP(Ccr2 sufficient) or RFP/RFP(Ccr2 deficient) with SARS-CoV-2 intranasally analyzed pDCs. Blood pDCs RFP +and their decreased RFP/RFPmice at baseline. Over seven days after infection (LD 50), increased then blood, while increasingly progressively lungs both +/RFPand RFP/RFPmice. However, absolute lung ratios lung/blood markedly diminished, as survival, We propose mortality Ccr2-deficient may be due part inadequate leading local deficiencies type 1 III interferons, critical for defense against SARS-CoV-2.