Search results for "Stem and progenitor cells"
showing 7 items of 7 documents
Cellular and molecular basis of the imbalance between vascular damage and repair in ageing and age-related diseases: As biomarkers and targets for ne…
2016
Preclinical and clinical studies suggest that specific subsets of cells isolated from the peripheral blood, play an essential role in the imbalance of damage and repair during age-associated diseases, such as metabolic syndrome, diabetes, atherosclerosis, neurodegenerative diseases, osteoporosis and cancer. Endogenous regeneration of the vessel wall involves cells of the vascular wall, inflammatory cells, circulating precursors, and mature endothelial cells, which are capable to restore the endothelium in a concerted interaction. Early detection of such imbalances with specific biomarkers may reduce age-associated diseases and subsequent cardiovascular events. Likewise, new strategies have …
Systemic Candidiasis and TLR2 Agonist Exposure Impact the Antifungal Response of Hematopoietic Stem and Progenitor Cells.
2018
We have previously demonstrated that Candida albicans induces differentiation of hematopoietic stem and progenitor cells (HSPCs) toward the myeloid lineage both in vitro and in vivo in a TLR2- and Dectin-1-dependent manner, giving rise to functional macrophages. In this work, we used an ex vivo model to investigate the functional consequences for macrophages derived from HSPCs in vivo-exposed to Pam3CSK4 (a TLR2 agonist) or C. albicans infection. Short in vivo treatment of mice with Pam3CSK4 results in a tolerized phenotype of ex vivo HSPC-derived macrophages, whereas an extended Pam3CSK4 treatment confers a trained phenotype. Early during candidiasis, HSPCs give rise to macrophages trained…
TLR2 and Dectin-1 Signaling in Mouse Hematopoietic Stem and Progenitor Cells Impacts the Ability of the Antigen Presenting Cells They Produce to Acti…
2020
Microbial recognition by pattern recognition receptors (PRRs) expressed on hematopoietic stem and progenitor cells (HSPCs) not only activates myelopoiesis but also programs the function of the monocytes and macrophages they produce. For instance, changes in HSPC programming modify the ability of macrophages derived from them to produce inflammatory cytokines. While HSPCs exposed to a TLR2 agonist give rise to tolerized macrophages (lower proinflammatory cytokine production), HSPCs treated with Dectin-1 ligands produce trained macrophages (higher proinflammatory cytokine production). However, nothing is known about the impact of HSPC exposure to microbes on the function of antigen presenting…
Direct Toll-Like Receptor-Mediated Stimulation of Hematopoietic Stem and Progenitor Cells Occurs In Vivo and Promotes Differentiation Toward Macropha…
2012
Abstract As Toll-like receptors (TLRs) are expressed by hematopoietic stem and progenitor cells (HSPCs), they may play a role in hematopoiesis in response to pathogens during infection. We show here that TLR2, TLR4, and TLR9 agonists (tripalmitoyl-S-glyceryl-L-Cys-Ser-(Lys)4 [Pam3CSK4], lipopolysaccharide [LPS], and CpG oligodeoxynucleotide [ODN]) induce the in vitro differentiation of purified murine lineage negative cells (Lin−) as well as HSPCs (identified as Lin− c-Kit+ Sca-1+ IL-7Rα− [LKS] cells) toward macrophages (Mph), through a myeloid differentiation factor 88 (MyD88)-dependent pathway. In order to investigate the possible direct interaction of soluble microorganism-associated mol…
Dectin-1 Stimulation of Hematopoietic Stem and Progenitor Cells Occurs In Vivo and Promotes Differentiation Toward Trained Macrophages via an Indirec…
2020
Invasive candidiasis is an increasingly frequent cause of serious and often fatal infections. Understanding host defense is essential to design novel therapeutic strategies to boost immune protection against Candida albicans. In this article, we delve into two new concepts that have arisen over the last years: (i) the delivery of myelopoiesis-inducing signals by microbial components directly sensed by hematopoietic stem and progenitor cells (HSPCs) and (ii) the concept of “trained innate immunity” that may also apply to HSPCs. We demonstrate that dectin-1 ligation in vivo activates HSPCs and induces their differentiation to trained macrophages by a cell-autonomous indirect mechanism. This p…
Role of PRRs (TLR2 and Dectin-1) in hematopoietic stem and progenitor cell differentiation: implications in protection against Candida albicans infec…
2020
Detection of infection by hematopoietic stem and progenitor cells (HSPCs) is essential to replace myeloid cells consumed during the immune response. HSPCs express some functional pattern recognition receptors involved in the recognition of Candida albicans. In this context, our group has previously demonstrated that C. albicans yeasts induce proliferation and differentiation of HSPCs via TLR2 and Dectin-1. In the present PhD thesis, we used in vitro and ex vivo models of HSPC differentiation to investigate the functional consequences for mature myeloid cells of exposure of HSPCs to PAMPs or C. albicans yeasts. In vitro experiments show that murine HSPCs continuously exposed to TLR2 or TLR4 …
Role of hematopoietic stem and progenitor cells in training immunity against infection
2022
During an infection, haematopoiesis is altered to increase the output of mature myeloid cells to fight off the pathogen. It has been demonstrated that the detection of pattern recognition receptor agonists by hematopoietic stem and progenitor cells (HSPCs) induces their differentiation towards mature myeloid cells with modified phenotypes. In the present PhD thesis, we show that an in vitro transient exposure of HSPCs to live Candida albicans cells is sufficient to induce a trained phenotype of the macrophages they produce in a dectin-1- and TLR2-dependent manner. Additionally, we use an HSPC transplantation mouse model to demonstrate that the direct interaction of β-glucans and their recep…