Epigenetic memory of coronavirus infection in innate immune cells and their progenitors, 2023, Cheong et al.

Epigenetic memory of coronavirus infection in innate immune cells and their progenitors
Jin-Gyu Cheong; Arjun Ravishankar; Siddhartha Sharma; Christopher N. Parkhurst; Simon A. Grassmann; Claire K. Wingert; Paoline Laurent; Sai Ma; Lucinda Paddock; Isabella C. Miranda; Emin Onur Karakaslar; Djamel Nehar-Belaid; Asa Thibodeau; Michael J. Bale; Vinay K. Kartha; Jim K. Yee; Minh Y. Mays; Chenyang Jiang; Andrew W. Daman; Alexia Martinez de Paz; Dughan Ahimovic; Victor Ramos; Alexander Lercher; Erik Nielsen; Sergio Alvarez-Mulett; Ling Zheng; Andrew Earl; Alisha Yallowitz; Lexi Robbins; Elyse LaFond; Karissa L. Weidman; Sabrina Racine-Brzostek; He S. Yang; David R. Price; Louise Leyre; André F. Rendeiro; Hiranmayi Ravichandran; Junbum Kim; Alain C. Borczuk; Charles M. Rice; R. Brad Jones; Edward J. Schenck; Robert J. Kaner; Amy Chadburn; Zhen Zhao; Virginia Pascual; Olivier Elemento; Robert E. Schwartz; Jason D. Buenrostro; Rachel E. Niec; Franck J. Barrat; Lindsay Lief; Joseph C. Sun; Duygu Ucar; Steven Z. Josefowicz

Inflammation can trigger lasting phenotypes in immune and non-immune cells. Whether and how human infections and associated inflammation can form innate immune memory in hematopoietic stem and progenitor cells (HSPC) has remained unclear.

We found that circulating HSPC, enriched from peripheral blood, captured the diversity of bone marrow HSPC, enabling investigation of their epigenomic reprogramming following coronavirus disease 2019 (COVID-19). Alterations in innate immune phenotypes and epigenetic programs of HSPC persisted for months to 1 year following severe COVID-19 and were associated with distinct transcription factor (TF) activities, altered regulation of inflammatory programs, and durable increases in myelopoiesis. HSPC epigenomic alterations were conveyed, through differentiation, to progeny innate immune cells. Early activity of IL-6 contributed to these persistent phenotypes in human COVID-19 and a mouse coronavirus infection model.

Epigenetic reprogramming of HSPC may underlie altered immune function following infection and be broadly relevant, especially for millions of COVID-19 survivors.

Link | PDF (Cell) paywall

 

See earlier threads —

Monocyte migration profiles define disease severity in acute COVID-19 and unique features of long COVID (2023)
Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19 (2022)

For some related open access articles, see also —

Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines (2022, Genome Medicine)
Monocyte and haematopoietic progenitor reprogramming as common mechanism underlying chronic inflammatory and cardiovascular diseases (2018, European Heart Journal)

 

NIH news release about this study, https://www.nih.gov/news-events/new...y-lead-long-term-innate-immune-system-changes

 

• BMMC = bone marrow mononuclear cells
• GMP = granulocyte-monocyte progenitors
• HSPC = hematopoietic stem and progenitor cells
• PBMC = peripheral blood mononuclear cells

Selected abbreviated quotes from the discussion (re-ordered) —

Circulating HSPC analysis: An approach to studying HSPC in a post-COVID-19 cohort

Persistence of HSPC alterations and molecular phenotypes post-COVID-19

Implications for post-infection pathology and recovery

IL-6 regulates post-infection phenotypes

Commenting

 

Comment in Long-COVID-19: the persisting imprint of SARS-CoV-2 infections on the innate immune system (2023, Nature Signal Transduction and Targeted Therapy) —

 

Comment in Hematopoietic memory of severe COVID-19 infection (2023, Nature Cell Research) —

 

I've posted a review article for trained innate immunity in Defining trained immunity and its role in health and disease (2020, Nature Reviews Immunology)