CSF1R defines the mononuclear phagocyte system lineage in human blood in health and COVID-19

Theo W. Combes, Federica Orsenigo, Alexander Stewart, A. S.Jeewaka R. Mendis, Deborah Dunn-Walters, Siamon Gordon, Fernando O. Martinez*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

10 Scopus citations

Abstract

Mononuclear phagocytes defend tissues, present antigens, and mediate recovery and healing. To date, we lack a marker to unify mononuclear phagocytes in humans or that informs us about their origin. Here, we reassess mononuclear phagocyte ontogeny in human blood through the lineage receptor CSF1R, in the steady state and in COVID-19. We define CSF1R as the first sensitive and reproducible pan-phagocyte lineage marker, to identify and enumerate all conventional monocytes, and the myeloid dendritic cells. In the steady state, CSF1R is sufficient for sorting and immuno-magnetic isolation. In pathology, changes in CSF1R are more sensitive than CD14 and CD16. In COVID-19, a significant drop in membrane CSF1R is useful for stratifying patients, beyond the power of cell categories published thus far, which fail to capture COVID-19 specific events. Importantly, CSF1R defines cells which are neither conventional monocytes nor DCs, which are missed in published analysis. CSF1R decrease can be linked ex vivo to high CSF1 levels. Blood assessment of CSF1R+ cells opens a developmental window to the Mononuclear Phagocyte System in transit from bone marrow to tissues, supports isolation and phenotypic characterisation, identifies novel cell types, and singles out CSF1R inhibition as therapeutic target in COVID-19 and other diseases.

Original languageEnglish
Article numberltab003
JournalImmunotherapy Advances
Volume1
Issue number1
DOIs
StatePublished - 01 01 2021

Bibliographical note

Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press on behalf of the British Society for Immunology.

Keywords

  • COVID-19
  • CSF1R
  • blood
  • dendritic cells
  • human
  • monocyte

Fingerprint

Dive into the research topics of 'CSF1R defines the mononuclear phagocyte system lineage in human blood in health and COVID-19'. Together they form a unique fingerprint.

Cite this