The human vascular system, comprising endothelial cells (ECs) and mural cells, covers a vast surface area in the body, providing a critical interface between blood and tissue environments. Functional differences exist across specific vascular beds, but their molecular determinants across tissues remain largely unknown. In this study, we integrated single-cell transcriptomics data from 19 human organs and tissues and defined 42 vascular cell states from approximately 67,000 cells (62 donors), including angiotypic transitional signatures along the arterial endothelial axis from large to small caliber vessels.
View Article and Find Full Text PDFIntroduction: During infection, bone marrow (BM) hematopoiesis is reprogrammed toward myeloid cell production, a mechanism named emergency myelopoiesis. In addition to replenishing myeloid cells, emergency myelopoiesis has been linked to trained immunity, a process that allows enhanced innate immune responses to secondary challenges. Although hematopoietic alterations during tuberculosis (TB) have been described and may colonize the BM, studies using the mouse model of infection and the laboratory reference strain H37Rv have demonstrated limited emergency myelopoiesis and trained immunity.
View Article and Find Full Text PDFTuberculosis (TB), one of the deadliest threats to human health, is mainly caused by 2 highly related and human-adapted bacteria broadly known as Mycobacterium tuberculosis and Mycobacterium africanum. Whereas M. tuberculosis is widely spread, M.
View Article and Find Full Text PDFIn emergency myelopoiesis (EM), expansion of the myeloid progenitor compartment and increased myeloid cell production are observed and often mediated by the pro-inflammatory cytokine interferon gamma (IFN-γ). Interleukin-10 (IL-10) inhibits IFN-γ secretion, but paradoxically, its therapeutic administration to humans causes hematologic changes similar to those observed in EM. In this work, we use different in vivo systems, including a humanized immune system mouse model, to show that IL-10 triggers EM, with a significant expansion of the myeloid progenitor compartment and production of myeloid cells.
View Article and Find Full Text PDFGlycans display increasingly recognized roles in pathological contexts, however, their impact in the host-pathogen interplay in many infectious diseases remains largely unknown. This is the case for tuberculosis (TB), one of the ten most fatal diseases worldwide, caused by infection of the bacteria . We have recently reported that perturbing the core-2 -glycans biosynthetic pathway increases the host susceptibility to infection, by disrupting the neutrophil homeostasis and enhancing lung pathology.
View Article and Find Full Text PDFGenetic diversity of Mycobacterium tuberculosis affects immune responses and clinical outcomes of tuberculosis (TB). However, how bacterial diversity orchestrates immune responses to direct distinct TB severities is unknown. Here we study 681 patients with pulmonary TB and show that M.
View Article and Find Full Text PDFModulation of immunity and disease by glycans is increasingly recognized. However, how host glycosylation shapes and is shaped by tuberculosis remains poorly understood. We show that deficiency in the glucosaminyl (N-acetyl) transferase 1 (Gcnt1), a key enzyme for core-2 O-glycans biosynthesis, drives susceptibility to Mycobacterium tuberculosis infection.
View Article and Find Full Text PDFTuberculosis remains a public health problem and a main cause of death to humans. Both and cause tuberculosis. In contrast to , which is geographically spread, is restricted to West Africa.
View Article and Find Full Text PDFGerminal center (GC) responses are controlled by T follicular helper (T) and T follicular regulatory (T) cells and are crucial for the generation of high-affinity antibodies. Although the biology of human circulating and tissue T cells has been established, the relationship between blood and tissue T cells defined as CXCR5Foxp3 T cells remains elusive. We found that blood T cells are increased in Sjögren syndrome, an autoimmune disease with ongoing GC reactions, especially in patients with high autoantibody titers, as well as in healthy individuals upon influenza vaccination.
View Article and Find Full Text PDFIt has long been known that CD4 T cells are necessary to provide help to B cells, triggering a germinal centre (GC) reaction where affinity maturation and isotype switching occur. However, the nature of the dedicated CD4 helper T cells, known as T follicular helper (Tfh), was only recently described. Here, we review the biology and function of the recently described T follicular regulatory (Tfr) cells, another CD4 T-cell population also found within GCs but with regulatory function and characteristics.
View Article and Find Full Text PDFImmunization leads to the formation of germinal centres (GCs) that contain both T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Whether T-cell receptor (TCR) specificity defines the differential functions of Tfh and Tfr cells is unclear. Here we show that antigen-specific T cells after immunization are preferentially recruited to the GC to become Tfh cells, but not Tfr cells.
View Article and Find Full Text PDFMethods Mol Biol
December 2015
Flow cytometry is a technology that allows multiparametric analysis of individual cells. As a consequence, it is among the most commonly used tools for the study of immune cells. It is useful both for the study of ex vivo cell populations isolated from experimental animals or human tissue and for characterizing the phenotype of cultured cells.
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