Title | Epigenetic memory of coronavirus infection in innate immune cells and their progenitors. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Cheong J-G, Ravishankar A, Sharma S, Parkhurst CN, Grassmann SA, Wingert CK, Laurent P, Ma S, Paddock L, Miranda IC, Karakaslar EOnur, Nehar-Belaid D, Thibodeau A, Bale MJ, Kartha VK, Yee JK, Mays MY, Jiang C, Daman AW, de Paz AMartÃnez, Ahimovic D, Ramos V, Lercher A, Nielsen E, Alvarez-Mulett S, Zheng L, Earl A, Yallowitz A, Robbins L, LaFond E, Weidman KL, Racine-Brzostek S, Yang HS, Price DR, Leyre L, Rendeiro AF, Ravichandran H, Kim J, Borczuk AC, Rice CM, R Jones B, Schenck EJ, Kaner RJ, Chadburn A, Zhao Z, Pascual V, Elemento O, Schwartz RE, Buenrostro JD, Niec RE, Barrat FJ, Lief L, Sun JC, Ucar D, Josefowicz SZ |
Journal | Cell |
Volume | 186 |
Issue | 18 |
Pagination | 3882-3902.e24 |
Date Published | 2023 Aug 31 |
ISSN | 1097-4172 |
Keywords | Animals, Cell Differentiation, COVID-19, Disease Models, Animal, Epigenetic Memory, Hematopoietic Stem Cells, Humans, Inflammation, Mice, Monocytes, Post-Acute COVID-19 Syndrome, Trained Immunity |
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. |
DOI | 10.1016/j.cell.2023.07.019 |
Alternate Journal | Cell |
PubMed ID | 37597510 |
PubMed Central ID | PMC10638861 |
Grant List | R01 AI142086 / AI / NIAID NIH HHS / United States R01 AI161444 / AI / NIAID NIH HHS / United States U19 AI144301 / AI / NIAID NIH HHS / United States R25 CA233208 / CA / NCI NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States UL1 TR002384 / TR / NCATS NIH HHS / United States R01 AI148416 / AI / NIAID NIH HHS / United States R01 DK121072 / DK / NIDDK NIH HHS / United States RM1 GM139738 / GM / NIGMS NIH HHS / United States R01 AI132447 / AI / NIAID NIH HHS / United States |
Related Faculty:
Steven Josefowicz, Ph.D. Amy Chadburn, M.D.