Kondratyeva Liya G, Rakitina Olga A, Pleshkan Victor V, Kuzmich Alexey I, Linge Irina A, Kondratieva Sofia A, Snezhkov Eugene V, Alekseenko Irina V, Sverdlov Eugene D
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow 117997, Russia.
National Research Center "Kurchatov Institute", Moscow 123182, Russia.
Cells. 2024 Dec 11;13(24):2043. doi: 10.3390/cells13242043.
It is established that BCG vaccination results in the development of both a specific immune response to mycobacterial infections and a nonspecific (heterologous) immune response, designated as trained immunity (TRIM), to other pathogens. We hypothesized that local BCG immunization may induce an early immune response in bone marrow and spleen innate immunity cells. The early transcriptomic response of various populations of innate immune cells, including monocytes, neutrophils, and natural killer (NK) cells, to BCG vaccination was examined. To this end, C57Bl/6J mice were subcutaneously immunized with 10 CFU of BCG. Three days following BCG administration, the three cell populations were collected from the control and BCG-vaccinated groups using FACS. All cell populations obtained were utilized for the preparation and sequencing of RNA-seq libraries. The analysis of FACS data revealed an increase in the proportion of splenic NK cells and monocytes 3 days post-vaccination. Transcriptomic analysis revealed the deregulation of genes associated with the regulation of immune response (according to Gene Ontology terms) in NK cells, monocytes, and unsorted bone marrow cells. Two NK cell-specific immune ligands (Tnfsf14 and S100a8) and two bone marrow-specific immune receptors (C5ar1 and Csf2rb) were identified among differentially expressed genes. No alterations were identified in neutrophils in either their percentage or at the transcriptomic level. Thus, in this study, we demonstrated that BCG vaccination provides an early increase in the proportion of murine bone marrow and spleen immune cell populations, as well as transcriptomic alterations in monocytes, NK cells, and non-sorted bone marrow cells. This early innate immune response may be beneficial for enhancing TRIM.
已证实，卡介苗接种会导致对分枝杆菌感染产生特异性免疫反应，并对其他病原体产生非特异性（异源）免疫反应，即所谓的训练免疫（TRIM）。我们假设局部卡介苗免疫可能会在骨髓和脾脏固有免疫细胞中诱导早期免疫反应。研究了包括单核细胞、中性粒细胞和自然杀伤（NK）细胞在内的各种固有免疫细胞群体对卡介苗接种的早期转录组反应。为此，用10 CFU卡介苗对C57Bl/6J小鼠进行皮下免疫。卡介苗接种三天后，使用荧光激活细胞分选术（FACS）从对照组和卡介苗接种组收集这三种细胞群体。所获得的所有细胞群体都用于制备RNA测序文库并进行测序。FACS数据分析显示接种疫苗三天后脾脏NK细胞和单核细胞的比例增加。转录组分析揭示了NK细胞、单核细胞和未分选的骨髓细胞中与免疫反应调节相关的基因失调（根据基因本体论术语）。在差异表达基因中鉴定出两种NK细胞特异性免疫配体（Tnfsf14和S100a8）和两种骨髓特异性免疫受体（C5ar1和Csf2rb）。在中性粒细胞的百分比或转录组水平上均未发现改变。因此，在本研究中，我们证明了卡介苗接种可使小鼠骨髓和脾脏免疫细胞群体的比例早期增加，以及单核细胞、NK细胞和未分选骨髓细胞中的转录组改变。这种早期固有免疫反应可能有助于增强训练免疫（TRIM）。
