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: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:Trained immunity is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to certain microbial components, altering their responses to future exposures. This study profiled the transcriptomes of human monocytes responding to two different BCG vaccine strains.
Project description:The capacity of innate immune cells to build immunological memory after a first encounter with certain pathogens or vaccines that allow them to respond stronger to reinfection is referred to as “trained immunity”. Despite few studies highlighting an important role for trained immunity in protection during COVID-19 infection or vaccination, no study so far has shown whether SARS-CoV-2 can train innate immune cells to respond stronger to a second stimuli. The aim of this study was to investigate whether this virus can induce trained immunity in human monocytes. To this purpose we used monocytes from healthy donors and exposed them to inactivated (i) SARS -CoV-2 for 24 hours followed by a resting period of several days in medium only and restimulation on day 6. On day 6, to evaluate the effects of iSARS-CoV-2 training on monocyte gene expression, transcriptomic analysis of human monocytes, before or 3h after LPS stimulation, was done. Our data provide the transcriptional profile of untrained and trained monocytes with iSARS-CoV-2.
Project description:Trained immunity is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to certain microbial components, altering their responses to future exposures. This study profiled the distribution of two active histone modifications (H3K27ac and H3K4me1) of human monocytes responding to two different BCG vaccine strains.
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.
Project description:Trained immunity is a phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to certain microbial components, altering their responses to future exposures. This study profiled the transcriptome of human monocytes and in vitro differentiated macrophages, exposed to a combination of LPS, BG, DMI, or Itaconate.
Project description:Trained immunity is a phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to certain microbial components, altering their responses to future exposures. This study profiled the transcriptome of human macrophages trained with IL4 and then re-exposed to lipopolysaccharide.