Evidence map›Paper›PMID 36085197›Full record

ArticleCell discovery2022

Surface translocation of ACE2 and TMPRSS2 upon TLR4/7/8 activation is required for SARS-CoV-2 infection in circulating monocytes.

Yi Yao, Kalpana Subedi, Tingting Liu, Namir Khalasawi, Carla Diana Pretto-Kernahan, Jesse William Wotring, Jie Wang, Congcong Yin, Aimin Jiang, Chunmei Fu and 9 more

Open access · goldAbstract read
In one paragraph

Article in Cell discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.3field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
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  7. Deep insight into cytokine storm: from pathogenesis to treatment.Signal transduction and targeted therapy · 2025
    Review
  8. The Functions of SARS-CoV-2 Receptors in Diabetes-Related Severe COVID-19.International journal of molecular sciences · 2024
    Review
  9. Article
  10. Review
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  14. COVID-19 associated mold infections: Review of COVID-19 associated pulmonary aspergillosis and mucormycosis.Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi · 2023
    Review
  15. Article
  16. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 2 institutions in 1 country.

Yi Yao *Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health System, Detroit, MI, USA.
Kalpana Subedi *Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health System, Detroit, MI, USA.
Tingting LiuCenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health System, Detroit, MI, USA.
Namir KhalasawiCenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health System, Detroit, MI, USA.
Carla Diana Pretto-KernahanInternal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA.
Jesse William WotringInternal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA.
Jie WangCenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health System, Detroit, MI, USA.
Congcong YinCenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health System, Detroit, MI, USA.
Aimin JiangCenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health System, Detroit, MI, USA.
Chunmei FuCenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health System, Detroit, MI, USA.
Peter DimitrionCenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health System, Detroit, MI, USA.
Jia LiDepartment of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA.
Jesse VeenstraCenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health System, Detroit, MI, USA.
Qijun YiCenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health System, Detroit, MI, USA.
Kathy McKinnonDivision of Rheumatology, Department of Internal Medicine, Henry Ford Health System, Detroit, MI, USA.
John Ernest McKinnonDivision of Infectious Diseases, Department of Internal Medicine, Henry Ford Health System, Detroit, MI, USA.
Jonathan Zachary SextonInternal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA. jzsexton@umich.edu.
Li ZhouCenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health System, Detroit, MI, USA. lzhou1@hfhs.org.
Qing-Sheng MiCenter for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health System, Detroit, MI, USA. QMI1@hfhs.org.ORCID http://orcid.org/0000-0002-1411-6827
Henry Ford Health System · USUniversity of Michigan · US

Funding

Michigan Institute for Clinical and Health Research (MICHR)UL1TR002240 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LUMENG, JULIE C, MASHOUR, GEORGE ALEXANDER · 2017 to 2022
$54.9M
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) UL1TR002240NCATS NIH HHS UL1 TR002240
6 · The paper itself

Abstract

Infection of human peripheral blood cells by SARS-CoV-2 has been debated because immune cells lack mRNA expression of both angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease type 2 (TMPRSS2). Herein we demonstrate that resting primary monocytes harbor abundant cytoplasmic ACE2 and TMPRSS2 protein and that circulating exosomes contain significant ACE2 protein. Upon ex vivo TLR4/7/8 stimulation, cytoplasmic ACE2 was quickly translocated to the monocyte cell surface independently of ACE2 transcription, while TMPRSS2 surface translocation occurred in conjunction with elevated mRNA expression. The rapid translocation of ACE2 to the monocyte cell surface was blocked by the endosomal trafficking inhibitor endosidin 2, suggesting that endosomal ACE2 could be derived from circulating ACE2-containing exosomes. TLR-stimulated monocytes concurrently expressing ACE2 and TMPRSS2 on the cell surface were efficiently infected by SARS-CoV-2, which was significantly mitigated by remdesivir, TMPRSS2 inhibitor camostat, and anti-ACE2 antibody. Mass cytometry showed that ACE2 surface translocation in peripheral myeloid cells from patients with severe COVID-19 correlated with its hyperactivation and PD-L1 expression. Collectively, TLR4/7/8-induced ACE2 translocation with TMPRSS2 expression makes circulating monocytes permissive to SARS-CoV-2 infection.

Identifiers

PMID36085197
PMCPMC9462622
OpenAlexW4295067041

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.