Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19, 2022, Maher et al

[SNT Gatchaman]

Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19
Maher, Allison K; Burnham, Katie L; Jones, Emma M; Tan, Michelle MH; Saputil, Rocel C; Baillon, Laury; Selck, Claudia; Giang, Nicolas; Argüello, Rafael; Pillay, Clio; Thorley, Emma; Short, Charlotte-Eve; Quinlan, Rachael; Barclay, Wendy S; Cooper, Nichola; Taylor, Graham P; Davenport, Emma E; Dominguez-Villar, Margarita

Although alterations in myeloid cells have been observed in COVID-19, the specific underlying mechanisms are not completely understood. Here, we examine the function of classical CD14+ monocytes in patients with mild and moderate COVID-19 during the acute phase of infection and in healthy individuals.

Monocytes from COVID-19 patients display altered expression of cell surface receptors and a dysfunctional metabolic profile that distinguish them from healthy monocytes. Secondary pathogen sensing ex vivo leads to defects in pro-inflammatory cytokine and type-I IFN production in moderate COVID-19 cases, together with defects in glycolysis.

COVID-19 monocytes switch their gene expression profile from canonical innate immune to pro-thrombotic signatures and are functionally pro-thrombotic, both at baseline and following ex vivo stimulation with SARS-CoV-2. Transcriptionally, COVID-19 monocytes are characterized by enrichment of pathways involved in hemostasis, immunothrombosis, platelet aggregation and other accessory pathways to platelet activation and clot formation.

These results identify a potential mechanism by which monocyte dysfunction may contribute to COVID-19 pathology.

Link | PDF (Nature Communications)

 

[SNT Gatchaman]

See also Monocyte and haematopoietic progenitor reprogramming as common mechanism underlying chronic inflammatory and cardiovascular diseases (2018)

 

[boolybooly]

That is very interesting as it strikes me that if monocyte reprogramming can commonly increase thrombogenicity and inflammation as a response of the monocytes rather than specifically due to a particular pathogen, it looks like a candidate process which could explain some of the symptoms of ME onset after infection and the ways ME changes as it ages.

The fact that EBV targets these cells and is associated with a proportion of ME cases increases the sense this might be something we need to understand better.

EDIT+
Infection of Primary Human Monocytes by Epstein-Barr Virus
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC111749/

 

[SNT Gatchaman]

Technique included SCENITH: A Flow Cytometry-Based Method to Functionally Profile Energy Metabolism with Single-Cell Resolution (2020)

 

[SNT Gatchaman]

See also Epigenetic memory of coronavirus infection in innate immune cells and their progenitors (2023)