Abstract
Recent studies in immunology have pointed out a process called trained immunity which is defined as the long-term functional reprogramming of cells of the innate immune system, induced by exogenous or endogenous challenges, leading to an enhanced response to a second challenge after a return to a non-activated state [1]. Trained immunity is known to be mediated by epigenetic reprogramming. In the immune system, epigenomic regulation has been observed during hematopoiesis, T cell memory, and B cell development. Additionally, epigenetic changes in monocytes and NK cells have been shown to imprint a form of innate immune memory [2]. Therefore, the concept of epigenetic imprinting on the immune system has gained particular relevance in the context of vaccination [3].
Fish red blood cells (RBCs) are gaining attention as a model for studying immune responses due to their active gene expression and participation in the innate and adaptive immune responses [4]. In the present work, we evaluated the epigenome of red blood cells (RBCs) from rainbow trout subjected to the viral hemorrhagic septicemia virus (VHSV), a DNA vaccine encoding the glycoprotein G of VHSV (pGVHSV), and an antiviral treatment based on green tea (Camellia sinensis). We used single cell Assay for Transposase-Accessible Chromatin sequencing (scATAC-seq), a high-throughput method used to identify open regions of chromatin across the genome, providing insight into the epigenetic landscape.
For this purpose, rainbow trout individuals were injected intramuscularly with the different stimuli mentioned above. After 3 days (or 5 days in the case of those individuals injected with pGVHSV), these individuals were sacrificed and RBCs were purified from blood from each individual. Then, we proceed with the characterization of chromatin accesibility by scATAC-seq.
The results demonstrated that vaccination and viral exposure showed distinct chromatin accessibility profiles, highlighting stimulated epigenomic remodeling of the immune response of RBCs, indicating activation of key regulatory elements.
References
1. Moorlag, S., et al., BCG Vaccination Induces Long-Term Functional Reprogramming of Human Neutrophils. Cell Rep, 2020. 33(7): p. 108387.
2. Wimmers, F., et al., The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination. Cell, 2021. 184(15): p. 3915-3935.e21.
3. Wimmers, F., et al., Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells. Nature Communications, 2018. 9(1).
4. Puente-Marin, S., et al., Potential Role of Rainbow Trout Erythrocytes as Mediators in the Immune Response Induced by a DNA Vaccine in Fish. Vaccines, 2019. 7(3): p. 60.
Acknowledgements
This work has been funded by MCIN-AEI CNS2022-135920 project.