While few will remember the last eighteen months with any great fondness, the memory of our immune cells represents a critical facet controlling long-lasting responses induced by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and exposure to vaccines. In an unforgettable study, researchers led by Liang Chen, Mark M. Davis, and Pengyuan Yang now demonstrate that chromatin remodeling fosters immunological memory in convalescing coronavirus disease COVID-19 patients.
To explore the links between chromatin and immune memory, the team performed single-cell transposase-accessible chromatin with sequencing (scATAC-seq) assays in the peripheral blood immune cells of ten convalescing patients who suffered SARS-CoV-2 infections and compared to six matched, uninfected donors. Furthermore, the authors developed a T-cell-centered approach (Ti-ATAC-seq) that permits single-cell analysis of cell-surface markers, T-cell receptor sequencing, and chromatin accessibility.
So let´s hear all the memorable points from this COVID-19 study from You, Chen, Zhang, Zhao, and Colleagues:
- Convalescing COVID-19 patients display significant alterations to most immune-cell compartments compared to healthy patients
- Innate immune cell analyses reveal that COVID-19 induces long-term adaptive changes in CD14+ and CD16+ monocytes (or “trained immunity”), which involves the generation of persistent open chromatin states at genes crucial to immune responses
- This immune memory permits innate immune cells to raise rapid inflammatory responses against future infections
- In the adaptive immune system, differential lineage trajectories in chromatin accessibility suggest an accelerated developmental program that produces antibody-producing plasma cells from immature B cells following B-cell expansion, thereby creating B-cell memory and ensuring long-term protection
- The study also identified a switch in the transcriptional machinery in convalescing patients, with the activator protein 1 (AP-1) transcription factors FOS and JUN inducing a change from maintenance and homeostasis (as observed in healthy patients) to B-cell activation, differentiation, and IgG class switch recombination
- Further evaluations of adaptive immune responses via the integrated analysis of T-cells suggests the clonal expansion of putative SARS-CoV-2-specific CD8+ T cells, in agreement with their role in initial viral control
- Chromatin remodeling associated with SARS-CoV-2 infection induces the development of effector CD8+ T cells and memory CD8+ T cells, with the latter allowing for long-term immune protection
Overall, the authors provide evidence that the global remodeling of the chromatin accessibility landscape in convalescing COVID-19 patients mediates the formation of immune memory and anticipate that a greater appreciation of the epigenomic regulation of host immune responses to SARS-CoV-2 infection and long-term immune protection may aid the development of therapeutics and evaluation of vaccine candidates.
Fill up your memory banks with all the details of this epigenomic COVID-19 study at Nature Cell Biology, June 2021.