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Epigenetic memory of coronavirus infection in innate immune cells and their progenitors.

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.

SUBMITTER: Cheong JG

PROVIDER: S-EPMC10638861 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Epigenetic memory of coronavirus infection in innate immune cells and their progenitors.

Cheong Jin-Gyu JG Ravishankar Arjun A Sharma Siddhartha S Parkhurst Christopher N CN Grassmann Simon A SA Wingert Claire K CK Laurent Paoline P Ma Sai S Paddock Lucinda L Miranda Isabella C IC Karakaslar Emin Onur EO Nehar-Belaid Djamel D Thibodeau Asa A Bale Michael J MJ Kartha Vinay K VK Yee Jim K JK Mays Minh Y MY Jiang Chenyang C Daman Andrew W AW Martinez de Paz Alexia A Ahimovic Dughan D Ramos Victor V Lercher Alexander A Nielsen Erik E Alvarez-Mulett Sergio S Zheng Ling L Earl Andrew A Yallowitz Alisha A Robbins Lexi L LaFond Elyse E Weidman Karissa L KL Racine-Brzostek Sabrina S Yang He S HS Price David R DR Leyre Louise L Rendeiro André F AF Ravichandran Hiranmayi H Kim Junbum J Borczuk Alain C AC Rice Charles M CM Jones R Brad RB Schenck Edward J EJ Kaner Robert J RJ Chadburn Amy A Zhao Zhen Z Pascual Virginia V Elemento Olivier O Schwartz Robert E RE Buenrostro Jason D JD Niec Rachel E RE Barrat Franck J FJ Lief Lindsay L Sun Joseph C JC Ucar Duygu D Josefowicz Steven Z SZ

Cell 20230818 18

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 epige ...[more]

PMID: 37597510

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Project description:IntroductionThe mechanisms underlying innate immune memory (trained immunity) comprise epigenetic reprogramming of transcriptional pathways associated with alterations of intracellular metabolism. While the mechanisms of innate immune memory carried out by immune cells are well characterized, such processes in non-immune cells, are poorly understood. The opportunistic pathogen, Staphylococcus aureus, is responsible for a multitude of human diseases, including pneumonia, endocarditis and osteomyelitis, as well as animal infections, including chronic cattle mastitis that are extremely difficult to treat. An induction of innate immune memory may be considered as a therapeutic alternative to fight S. aureus infection.MethodsIn the current work, we demonstrated the development of innate immune memory in non-immune cells during S. aureus infection employing a combination of techniques including Enzyme-linked immunosorbent assay (ELISA), microscopic analysis, and cytometry.ResultsWe observed that training of human osteoblast-like MG-63 cells and lung epithelial A549 cells with β-glucan increased IL-6 and IL-8 production upon a stimulation with S. aureus, concomitant with histones modifications. IL-6 and IL-8 production was positively correlated with an acetylation of histone 3 at lysine 27 (H3K27), thus suggesting epigenetic reprogramming in these cells. An addition of the ROS scavenger N-Acetylcysteine, NAC, prior to β-glucan pretreatment followed by an exposure to S. aureus, resulted in decreased IL-6 and IL-8 production, thereby supporting the involvement of ROS in the induction of innate immune memory. Exposure of cells to Lactococcus lactis resulted in increased IL-6 and IL-8 production by MG-63 and A549 cells upon a stimulation with S. aureus that was correlated with H3K27 acetylation, suggesting the ability of this beneficial bacterium to induce innate immune memory.DiscussionThis work improves our understanding of innate immune memory in non-immune cells in the context of S. aureus infection. In addition to known inducers, probiotics may represent good candidates for the induction of innate immune memory. Our findings may help the development of alternative therapeutic approaches for the prevention of S. aureus infection.

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Epigenetic memory of coronavirus infection in innate immune cells and their progenitors.

Publications

Epigenetic memory of coronavirus infection in innate immune cells and their progenitors.

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