Epigenetic memory of coronavirus infection in innate immune cells and their progenitors
Cheong, JG; Ravishankar, A; Sharma, S; et al., Cell
Published
August 2023
Journal
Cell
Abstract
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.
Authors
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
Keywords
COVID-19; IL-6; PASC; epigenetic memory; epigenome; hematopoietic stem and progenitor cells; monocytes; peripheral blood mononuclear cell progenitor input enrichment; post-acute sequelae SARS-CoV-2 infection; single-cell; trained immunity; transcriptome