TY - JOUR
T1 - Transcriptional Changes in CD16+ Monocytes May Contribute to the Pathogenesis of COVID-19
AU - Chilunda, Vanessa
AU - Martinez-Aguado, Pablo
AU - Xia, Li C.
AU - Cheney, Laura
AU - Murphy, Aniella
AU - Veksler, Veronica
AU - Ruiz, Vanessa
AU - Calderon, Tina M.
AU - Berman, Joan W.
N1 - Funding Information:
This work was funded by R01DA041931 (TC, JB), R01DA044584 (VC, LC, JB), R01DA048609 (LX, LC, JB), R01MH112391 (PM-A, TC, JB), T32AI007501(VR), T32GM007288 (VR), TL1TR002557 (AM), Innovation in Cancer Informatics Fund (LX) and Burroughs Wellcome Fund 342478 (VV).
Publisher Copyright:
© Copyright © 2021 Chilunda, Martinez-Aguado, Xia, Cheney, Murphy, Veksler, Ruiz, Calderon and Berman.
PY - 2021/5/24
Y1 - 2021/5/24
N2 - The COVID-19 pandemic has caused more than three million deaths globally. The severity of the disease is characterized, in part, by a dysregulated immune response. CD16+ monocytes are innate immune cells involved in inflammatory responses to viral infections, and tissue repair, among other functions. We characterized the transcriptional changes in CD16+ monocytes from PBMC of people with COVID-19, and from healthy individuals using publicly available single cell RNA sequencing data. CD16+ monocytes from people with COVID-19 compared to those from healthy individuals expressed transcriptional changes indicative of increased cell activation, and induction of a migratory phenotype. We also analyzed COVID-19 cases based on severity of the disease and found that mild cases were characterized by upregulation of interferon response and MHC class II related genes, whereas the severe cases had dysregulated expression of mitochondrial and antigen presentation genes, and upregulated inflammatory, cell movement, and apoptotic gene signatures. These results suggest that CD16+ monocytes in people with COVID-19 contribute to a dysregulated host response characterized by decreased antigen presentation, and an elevated inflammatory response with increased monocytic infiltration into tissues. Our results show that there are transcriptomic changes in CD16+ monocytes that may impact the functions of these cells, contributing to the pathogenesis and severity of COVID-19.
AB - The COVID-19 pandemic has caused more than three million deaths globally. The severity of the disease is characterized, in part, by a dysregulated immune response. CD16+ monocytes are innate immune cells involved in inflammatory responses to viral infections, and tissue repair, among other functions. We characterized the transcriptional changes in CD16+ monocytes from PBMC of people with COVID-19, and from healthy individuals using publicly available single cell RNA sequencing data. CD16+ monocytes from people with COVID-19 compared to those from healthy individuals expressed transcriptional changes indicative of increased cell activation, and induction of a migratory phenotype. We also analyzed COVID-19 cases based on severity of the disease and found that mild cases were characterized by upregulation of interferon response and MHC class II related genes, whereas the severe cases had dysregulated expression of mitochondrial and antigen presentation genes, and upregulated inflammatory, cell movement, and apoptotic gene signatures. These results suggest that CD16+ monocytes in people with COVID-19 contribute to a dysregulated host response characterized by decreased antigen presentation, and an elevated inflammatory response with increased monocytic infiltration into tissues. Our results show that there are transcriptomic changes in CD16+ monocytes that may impact the functions of these cells, contributing to the pathogenesis and severity of COVID-19.
KW - SARS-CoV-2
KW - cell movement
KW - inflammation
KW - non-classical monocytes
KW - single-cell transcriptomics
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U2 - 10.3389/fimmu.2021.665773
DO - 10.3389/fimmu.2021.665773
M3 - Article
C2 - 34108966
AN - SCOPUS:85107431198
SN - 1664-3224
VL - 12
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 665773
ER -