Project description:We generated BMDMs from aged C57BL/6J mice. BMDMs were treated with C.ablican derived β-glucan, which is known to induce trained immunity. mRNA was isolated form immune trained and control BMDMs using the Rneasy Kit from Qiagen. Library preparation and sequencing performed by Novogene. We found that trained immunity induced transcriptional changes in BMDMs from aged mice
Project description:We demonstrate that hydroxychloroquine inhibits trained immunity at the functional and epigenetic level and is accompanied by reduced expression of interferon-stimulated genes. Trained immunity comprises a functional adaptation induced by epigenetic reprogramming which facilitates the anti-viral innate immune response.
Project description:scRNAseq of monocytes from in vitro Trained immunity experiments stimulated by β-glucan (BG), uric acid (UA), muramyl dipeptide (MDP), oxidized low-density lipoprotein (oxLDL), or RPMI-Control, and respective samples restimulated with Lipopolysaccharide (LPS).
Project description:Antibiotic resistance and the pandemic of infectious diseases pose major hazards to human health. As a novel anti-infection strategy, trained immunity has a promising future. Recombinant Streptococcus pneumoniae Endopeptidase O (rPepO) is a novel trained immunity inducer that is a highly effective broad-spectrum anti-infective molecule. Here, we demonstrate that rPepO training induces a protective effect by improving the function of several immune cells. rPepO trains macrophages in the periphery to improve their immunological response. In addition, macrophage-derived complement C3 stimulates B lymphocytes to bolster the host's initial line of defense. While trained-macrophage-derived G-CSF changes the host's hematopoiesis and promotes central trained immunity. The "trained" label is found on freshly differentiated mononuclear macrophages, which also possess significantly enhanced anti-infective properties. Consequently, our research reveals that rPepO can induce peripheral and central trained immunity and possesses broad-spectrum and durable antimicrobial characteristics.
Project description:The main purpose of our study is to investigate if muscle damage in mdx mice alters the phenotype of macropahges at precursor level in the bone marrow. Here we show major remodeling of the epigenetic, metabolic and functional inflammatory profiles of monocyte-derived macrophages from the bone marrow of mdx mice is TLR4-dependent. This altered phenotype of mdx BMDM demonstrates the hallmark features of trained immunity, including being transmissible and long-lasting after bone marrow transplantation to non-dystrophic mice.
Project description:Induction of trained immunity by beta-glucan has been shown to promote transcriptomic alterations in myeloid cells. Monocytes are involved in the immune responses against tumors. In this study, we performed RNA sequencing in tumor-infiltrated monocytes from mice in order to investigate the impact of trained immunity on the transcriptomic profile of monocytes in the tumor setting.
Project description:Induction of trained immunity by beta-glucan affects myeloid cells and their bone marrow progenitors. In particular, broad alterations in the transcriptome of trained myeloid cells have been demonstrated. In this study, we performed RNA sequencing in GMP from beta-glucan treated mice, as compared to control-treated mice, in order to investigate the impact of trained immunity on the transcriptomic profile of GMP.
Project description:Monocyte differentiation into macrophages represents one of the cornerstone processes in innate host defense. In addition, immunological imprinting of either tolerance or trained immunity after an initial infection determines the functional fate of innate immune cells and the susceptibility of the host to secondary infections. Here we comprehensively characterize the epigenetic profiles of these functional states relative to healthy adult naM-CM-/ve monocytes. Inflammatory and metabolic pathways are strongly modulated in the derived macrophages, including decreased activation of inflammasome components. The cAMP-dependent signaling pathway is remodeled and adrenergic signaling was functionally implicated in trained innate immunity induction in vivo. Interestingly, M-oM-^AM-"-Glucan trains innate immune cells through extensive remodeling of distal regulatory region-bound histone acetylation, resulting in a sizeable exclusive epigenomic signature. Accordingly, genome-wide transcription factor footprint analysis reveals a specific transcription factor repertoire at trained cell-specific enhancers when recouped with epigenetic data, forming a rich hypothesis generator to manipulate innate immunity. Monocytes were pre-incubated either with cell culture medium (RPMI), M-NM-2-glucan (5M-BM-5g/mL) or with LPS (100ng/mL), for 24 hours in a total volume of 10 mL. After a wash-out, cells were cultured in RPMI supplemented with 10% human pool serum. Monocytes were collected at different time points (0 h and 6 d after treatment) and counted before further treatment for chromatin immunoprecipitation, RNA or DNaseI treatment. Different donor Buffycoats (BC) were used as independent replicates. Replicates were generated for all the profiles including ChIPseq,RNAseq and DNaseIseq.