A5088726380- T-cell and B-cell Immunology
- Tuberculosis Research and Epidemiology
- Immune Cell Function and Interaction
- Reproductive tract infections research
- Immunodeficiency and Autoimmune Disorders
- Immunotherapy and Immune Responses
- Mycobacterium research and diagnosis
- Immune responses and vaccinations
- Monoclonal and Polyclonal Antibodies Research
- Neonatal and Maternal Infections
- Streptococcal Infections and Treatments
- Immune Response and Inflammation
- Viral gastroenteritis research and epidemiology
- Reproductive System and Pregnancy
- vaccines and immunoinformatics approaches
- Antimicrobial Resistance in Staphylococcus
- Cervical Cancer and HPV Research
- Receptor Mechanisms and Signaling
- Viral Infections and Immunology Research
- Cellular transport and secretion
- Signaling Pathways in Disease
- Invertebrate Immune Response Mechanisms
- Urinary Tract Infections Management
- CAR-T cell therapy research
- Sphingolipid Metabolism and Signaling
Statens Serum Institut
2016-2025
University of Copenhagen
1994-2002
Institut Pasteur
1991
Centre National de la Recherche Scientifique
1991
Abstract We have identified new activating receptors of the Ig superfamily expressed on human myeloid cells, called TREM (triggering receptor cells). TREM-1 is selectively blood neutrophils and a subset monocytes up-regulated by bacterial LPS. Engagement triggers secretion IL-8, monocyte chemotactic protein-1, TNF-α induces neutrophil degranulation. Intracellularly, Ca2+ mobilization tyrosine phosphorylation extracellular signal-related kinase 1 (ERK1), ERK2 phospholipase C-γ. To mediate...
It is estimated that one-third of the world's population infected with Mycobacterium tuberculosis. Infection typically remains latent, but it can reactivate to cause clinical disease. The only vaccine, bovis bacillus Calmette-Guérin (BCG), largely ineffective, and ways enhance its efficacy are being developed. Of note, candidate booster vaccines currently under development have been designed improve BCG not prevent reactivation latent infection. Here, we demonstrate administering a...
Abstract Previously we have shown that Ag85B-ESAT-6 is a highly efficient vaccine against tuberculosis. However, because the ESAT-6 Ag also an extremely valuable diagnostic reagent, finding as effective does not contain high priority. Recently, identified novel protein expressed by Mycobacterium tuberculosis designated TB10.4. In most infected humans, TB10.4 strongly recognized, raising interest in potential candidate and substitute for ESAT-6. We now examined of this found vaccination with...
Summary Cationic liposomes are being used increasingly as efficient adjuvants for subunit vaccines but their precise mechanism of action is still unknown. Here, we investigated the adjuvant cationic based on synthetic amphiphile dimethyldioctadecylammonium (DDA). The did not have an effect maturation murine bone‐marrow‐derived dendritic cells (BM‐DCs) related to surface expression major histocompatibility complex (MHC) class II, CD40, CD80 and CD86. We found that ovalbumin (OVA) readily...
Abstract We have examined the intranasal administration of a vaccine against Mycobacterium tuberculosis (M.tb) consisting mucosal adjuvant LTK63 and Ag Ag85B-ESAT-6. Vaccination with LTK63/Ag85B-ESAT-6 gave strong sustained Th1 response mediated by IFN-γ-secreting CD4 cells, which led to long-lasting protection tuberculosis, equivalent that observed bacillus Calmette-Guérin (BCG) or Ag85B-ESAT-6 in dimethyldioctadecylammonium bromide/monophosphoryl lipid A. Because crucial element novel...
Background Previously we have shown that Ag85B-TB10.4 is a highly efficient vaccine against tuberculosis when delivered in Th1 inducing adjuvant based on cationic liposomes. Another adjuvant, which has very promising profile both preclinical and clinical trials, IC31®. In this study, examined the potential of IC31® for ability to induce protection infection with Mycobacterium tuberculosis. addition, if antigen dose could influence phenotype induced T cells. Methods Findings We found...
The ability to mount accelerated and efficient mucosal immune responses is critically important prevent the establishment of many infections. Secretion immunoglobulin A (IgA) a key component in this first line defense, but underlying cellular mechanisms are still not completely understood. We have evaluated different routes immunization examined requirements for IgA induction airway mucosa. demonstrate that subcutaneous priming with recombinant antigen T helper (Th)17-inducing adjuvant...
ABSTRACT Th17 cells are increasingly being recognized as an important T helper subset for immune-mediated protection, especially against pathogens at mucosal ports of entry. In several cases, it would thus be highly relevant to induce memory by vaccination. reported exhibit high plasticity and may not stably maintain their differentiation program once induced, questioning the possibility inducing durable memory. Accordingly, there is no consensus whether can established unless influenced...
Abstract The clinical development of an effective Chlamydia vaccine requires in-depth understanding how well protective pre-clinical immune signatures translate to humans. Here, we report a comparative immunological characterization CTH522/CAF®01 in female mice and We find range that from mouse human, including Th1/Th17 cytokine profile antibody functionality. identify vaccine-induced T cell epitopes, conserved among serovars, previously found infected individuals. Using the model, show...
Several receptors are downregulated by internalization after ligand binding. Regulation of T cell receptor (TCR) expression is an important step in activation, desensitization, and tolerance induction. One way cells regulate TCR phosphorylation/dephosphorylation the subunit clusters differentiation (CD)3γ. Thus, phosphorylation CD3γ serine 126 (S126) causes a downregulation TCR. In this study, we have analyzed motif three different systems parallel: context complete multimeric TCR; monomeric...
Signal-regulatory proteins (SIRPs) are cell-surface glycoproteins expressed on myeloid and neural cells that have been shown to recruit SH2 domain-containing protein phosphatase 1 (SHP-1) SHP-2 regulate receptor tyrosine kinase-coupled signaling. One SIRP of unknown function, designated beta 1, contains a short cytoplasmic domain lacks sequence motifs capable recruiting SHP-1 SHP-2. Using SIRP-specific mAb, we show is in monocytes dendritic associates with the signal transduction molecule...
Abstract Ig-like transcript 2 (ILT2)/leukocyte receptor 1 (LIR1) is a receptor, specific for MHC class I molecules, that inhibits lymphoid and myeloid cells. Here, we analyzed the molecular cellular mechanisms by which ILT2 modulates T cell activation in primary CTLs transfected lines. We found cross-linking with TCR activity of Src tyrosine kinase p56lck were required phosphorylation subsequent recruitment homology protein 1. In contrast, triggering resulted reduced TCRζ linker cells, led...
The ESX systems from Mycobacterium tuberculosis are responsible for the secretion of highly immunogenic proteins key importance bacterial survival and growth. two prototypic proteins, ESAT-6 (EsxA ESX-1) TB10.4 (EsxH ESX-3) share a lot characteristics regarding genome organization, size, antigenic properties, vaccine potential but molecules clearly have very different roles in physiology. To further investigate role as preventive post-exposure vaccines, we evaluated four fusion-protein...
Background The current vaccine against tuberculosis (TB), BCG, has failed to control TB worldwide and the protective efficacy is moreover limited 10–15 years. A that could efficiently boost a BCG-induced immune response thus prolong immunity would therefore have significant impact on global TB-burden. Methods/Findings In present study we show fusion protein HyVac4 (H4), consisting of mycobacterial antigens Ag85B TB10.4, given in adjuvant IC31® or DDA/MPL effectively boosted prolonged induced...
Transmembrane adapter proteins are a class of molecules that mediate signals from an extracellular receptor to the cytoplasm cell. We have cloned novel transmembrane protein called KAP10, approximately 10-kDa is encoded within 100 bp DAP12 locus on human chromosome 19. KAP10 predominantly expressed in immune cells, including NK T and monocytes. show unlike other proteins, binds phosphatidylinositol-3 kinase following phosphorylation cytoplasmic YINM motif, which results activation Akt. In...
Abstract Although infection with Mycobacterium tuberculosis (M.tb) induces a robust CD8 T cell response, the role of cells in defense against M.tb, and mechanisms behind induction cells, is still not clear. TB10.4 recently described Ag that expressed by both bacillus Calmette-Guérin (BCG) M.tb. In present study, we describe novel epitope TB10.4, TB10.43-11. We show TB10.43-11-specific are induced at onset throughout high numbers. TB10.43-11 were recruited to site CD44, TNF-α, IFN-γ....
The ESAT-6 (early secretory antigenic target) molecule is a very important target for T cell recognition during infection with Mycobacterium tuberculosis. Although contains numerous potential epitopes, the immune response often focused toward few immunodominant epitopes. By immunization individual overlapping synthetic peptides in cationic liposomes (cationic adjuvant formulation, CAF01) we demonstrate that several subdominant epitopes are not recognized H-2(d/b) mice either tuberculosis or...
Although CD4 T cells are crucial for defense against M.tb, it is still not clear whether the optimal response M.tb in fact involves both and CD8 cells. To test this, we used a new vaccine strategy that generated strong balanced cell consisting of cells.To compare responses Ag85B-TB10.4 (H4), H4 was delivered as subunit cationic liposomes (CAF01), expressed Ad5 (Ad-H4) or heterologous prime boost vaccination. H4/CAF01 induced primarily Ad-H4 gave predominantly response. In contrast,...
Abstract Each year, millions of people are infected with Streptococcus pyogenes, leading to an estimated 500,000 annual deaths worldwide. For unknown reasons, school-aged children have substantially higher infection rates than adults. The goal for this study was provide, our knowledge, the first detailed characterization human adaptive immune response against S. pyogenes in both and We report that all adults study, as well most children, showed immunity two conserved group A streptococci...
TCR down-regulation plays an important role in modulating T cell responses both during development and mature cells. Down-regulation of the is induced by engagement specific ligands and/or activation protein kinase C (PKC). We report here that ligand- PKC-induced mediated two distinct, independent mechanisms. Ligand-induced dependent on tyrosine kinases p56(lck) p59(fyn) but PKC CD3gamma leucine-based (L-based) internalization motif. In contrast, L-based motif p59(fyn). Finally, our data...
Infection with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), remains one leading causes mortality worldwide. The current "gold standard" vaccine bovis BCG has a limited efficacy that wanes over time. development to boost BCG-induced immunity is therefore highly active area research. Mucosal administration vaccines believed provide better protection against pathogens, such as M. invade host via mucosal surfaces. In this study we demonstrate an intranasal vaccine,...