TY - JOUR
T1 - Myeloid cell interferon responses correlate with clearance of SARS-CoV-2
AU - Singh, Dhiraj K.
AU - Aladyeva, Ekaterina
AU - Das, Shibali
AU - Singh, Bindu
AU - Esaulova, Ekaterina
AU - Swain, Amanda
AU - Ahmed, Mushtaq
AU - Cole, Journey
AU - Moodley, Chivonne
AU - Mehra, Smriti
AU - Schlesinger, Larry S.
AU - Artyomov, Maxim N.
AU - Khader, Shabaana A.
AU - Kaushal, Deepak
N1 - Funding Information:
The work described in this manuscript was supported by Washington University in St. Louis (S.A.K) for COVID-19 research, as well as and NIH award # R01AI123780 to S.A.K., and D.K., R01AI134236 to S.A.K. and D.K. and a COVID-19 supplement to it, an NIH award # R01AI134245 to S.M., COVID-19 research grant from San Antonio Medical Foundation to D.K.S and by institutional NIH awards P51OD111033 and U42OD010442 to the SNPRC, Texas Biomedical Research Institute. These funders had no role, however, in the design and execution of the experiments and the interpretation of data. The views expressed here are those of the authors and do not necessarily represent the views or official position of the funding agencies. The authors declare that no other financial conflict of interest exists.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Emergence of mutant SARS-CoV-2 strains associated with an increased risk of COVID-19-related death necessitates better understanding of the early viral dynamics, host responses and immunopathology. Single cell RNAseq (scRNAseq) allows for the study of individual cells, uncovering heterogeneous and variable responses to environment, infection and inflammation. While studies have reported immune profiling using scRNAseq in terminal human COVID-19 patients, performing longitudinal immune cell dynamics in humans is challenging. Macaques are a suitable model of SARS-CoV-2 infection. Our longitudinal scRNAseq of bronchoalveolar lavage (BAL) cell suspensions from young rhesus macaques infected with SARS-CoV-2 (n = 6) demonstrates dynamic changes in transcriptional landscape 3 days post- SARS-CoV-2-infection (3dpi; peak viremia), relative to 14-17dpi (recovery phase) and pre-infection (baseline) showing accumulation of distinct populations of both macrophages and T-lymphocytes expressing strong interferon-driven inflammatory gene signature at 3dpi. Type I interferon response is induced in the plasmacytoid dendritic cells with appearance of a distinct HLADR+CD68+CD163+SIGLEC1+ macrophage population exhibiting higher angiotensin-converting enzyme 2 (ACE2) expression. These macrophages are significantly enriched in the lungs of macaques at 3dpi and harbor SARS-CoV-2 while expressing a strong interferon-driven innate anti-viral gene signature. The accumulation of these responses correlated with decline in viremia and recovery.
AB - Emergence of mutant SARS-CoV-2 strains associated with an increased risk of COVID-19-related death necessitates better understanding of the early viral dynamics, host responses and immunopathology. Single cell RNAseq (scRNAseq) allows for the study of individual cells, uncovering heterogeneous and variable responses to environment, infection and inflammation. While studies have reported immune profiling using scRNAseq in terminal human COVID-19 patients, performing longitudinal immune cell dynamics in humans is challenging. Macaques are a suitable model of SARS-CoV-2 infection. Our longitudinal scRNAseq of bronchoalveolar lavage (BAL) cell suspensions from young rhesus macaques infected with SARS-CoV-2 (n = 6) demonstrates dynamic changes in transcriptional landscape 3 days post- SARS-CoV-2-infection (3dpi; peak viremia), relative to 14-17dpi (recovery phase) and pre-infection (baseline) showing accumulation of distinct populations of both macrophages and T-lymphocytes expressing strong interferon-driven inflammatory gene signature at 3dpi. Type I interferon response is induced in the plasmacytoid dendritic cells with appearance of a distinct HLADR+CD68+CD163+SIGLEC1+ macrophage population exhibiting higher angiotensin-converting enzyme 2 (ACE2) expression. These macrophages are significantly enriched in the lungs of macaques at 3dpi and harbor SARS-CoV-2 while expressing a strong interferon-driven innate anti-viral gene signature. The accumulation of these responses correlated with decline in viremia and recovery.
UR - http://www.scopus.com/inward/record.url?scp=85124057157&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-28315-7
DO - 10.1038/s41467-022-28315-7
M3 - Article
C2 - 35115549
AN - SCOPUS:85124057157
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 679
ER -