A5002591547- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Glycosylation and Glycoproteins Research
- Immunotherapy and Immune Responses
- Carbohydrate Chemistry and Synthesis
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- Circadian rhythm and melatonin
- Angiogenesis and VEGF in Cancer
- Diagnosis and treatment of tuberculosis
- Diabetes and associated disorders
- Inflammasome and immune disorders
- Infectious Diseases and Tuberculosis
- Acute Myeloid Leukemia Research
- Immunodeficiency and Autoimmune Disorders
- Phagocytosis and Immune Regulation
- Immune responses and vaccinations
- Hematological disorders and diagnostics
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- Galectins and Cancer Biology
Wellcome Sanger Institute
2024
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto
2018-2023
Universidade do Porto
2019-2023
University of Lisbon
2015-2017
Instituto Gulbenkian de Ciência
2015-2017
Abstract Immunization leads to the formation of germinal centres (GCs) that contain both T follicular helper (Tfh) and regulatory (Tfr) cells. Whether T-cell receptor (TCR) specificity defines differential functions Tfh Tfr cells is unclear. Here we show antigen-specific after immunization are preferentially recruited GC become cells, but not also proliferate efficiently on restimulation with same immunizing antigen in vitro . Ex vivo TCR repertoire analysis shows induces oligoclonal...
Germinal center (GC) responses are controlled by T follicular helper (Tfh) and regulatory (Tfr) cells crucial for the generation of high-affinity antibodies. Although biology human circulating tissue Tfh has been established, relationship between blood Tfr defined as CXCR5+Foxp3+ remains elusive. We found that increased in Sjögren syndrome, an autoimmune disease with ongoing GC reactions, especially patients high autoantibody titers, well healthy individuals upon influenza vaccination....
The immune system comprises multiple cell lineages and heterogeneous subsets found in blood tissues throughout the body. While human responses differ between sites over age, underlying sources of variation remain unclear as most studies are limited to peripheral blood. Here, we took a systems approach comprehensively profile RNA surface protein expression 1.25 million cells isolated from blood, lymphoid organs, mucosal 24 organ donors aged 20-75 years. We applied multimodal classifier...
Genetic diversity of Mycobacterium tuberculosis affects immune responses and clinical outcomes (TB). However, how bacterial orchestrates to direct distinct TB severities is unknown. Here we study 681 patients with pulmonary show that M. isolates from cases mild disease consistently induce robust cytokine in macrophages across multiple donors. By contrast, bacteria severe do not so. Secretion IL-1β a good surrogate the differences observed, thus classify strains as probable drivers different...
Within the thymus, thymic epithelial cells (TECs) provide dedicated stroma microenvironments for T cell development. Because TEC functionality is sensitive to aging and cytoablative therapies, unraveling molecular elements that coordinate their thymopoietic role has fundamental clinical implications. Particularly, selection of CD4 depends on interactions between TCRs expressed precursors self-peptides:MHC II complexes presented by cortical TECs (cTECs). Although...
Introduction During infection, bone marrow (BM) hematopoiesis is reprogrammed toward myeloid cell production, a mechanism named emergency myelopoiesis. In addition to replenishing cells, myelopoiesis has been linked trained immunity, process that allows enhanced innate immune responses secondary challenges. Although hematopoietic alterations during tuberculosis (TB) have described and Mycobacterium may colonize the BM, studies using mouse model of infection laboratory reference strain M....
Modulation of immunity and disease by glycans is increasingly recognized. However, how host glycosylation shapes shaped 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 infection. The increased Gcnt1 deficient mice was characterized extensive lung immune pathology, mechanistically related neutrophils. Uninfected presented bone marrow,...
In emergency myelopoiesis (EM), expansion of the myeloid progenitor compartment and increased cell production are observed often mediated by 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 those in EM. this work, we use different vivo systems, including a humanized immune system mouse model, show that IL-10 triggers EM, with significant cells....
Tuberculosis remains a public health problem and main cause of death to humans. Both Mycobacterium tuberculosis africanum tuberculosis. In contrast M. tuberculosis, which is geographically spread, restricted West Africa. Differences have also been found in the growth rate type disease caused by africanum, globally suggesting an attenuation this bacteria. study, we used mouse model infection follow dynamics terms bacterial burdens tissue pathology, as well immune response triggered. Our...
Glycans display increasingly recognized roles in pathological contexts, however, their impact the host-pathogen interplay many infectious diseases remains largely unknown. This is case for tuberculosis (TB), one of ten most fatal worldwide, caused by infection bacteria Mycobacterium tuberculosis. We have recently reported that perturbing core-2 O-glycans biosynthetic pathway increases host susceptibility to M. infection, disrupting neutrophil homeostasis and enhancing lung pathology. In...
Background: Acute myeloid leukemia (AML) is characterized by blood cytopenias at diagnosis. The loss of non-malignant hematopoiesis in AML driven part induced quiescence hematopoietic stem cells, scavenging growth factors, remodeling the bone marrow (BM) microenvironment and space occupancy. patients often present with severe anemia, regardless degree infiltration. However, mechanisms underlying erythropoiesis are poorly understood. Aims: To investigate how affected a main focus on study...