A5077310799- Research on Leishmaniasis Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Trypanosoma species research and implications
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Immune cells in cancer
- Urticaria and Related Conditions
- Parasites and Host Interactions
- T-cell and B-cell Immunology
- Autoimmune Bullous Skin Diseases
- Phagocytosis and Immune Regulation
- Monoclonal and Polyclonal Antibodies Research
- Reproductive System and Pregnancy
- Cell Adhesion Molecules Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Nitric Oxide and Endothelin Effects
- Immunotherapy and Immune Responses
- Inflammasome and immune disorders
- Cytokine Signaling Pathways and Interactions
- Macrophage Migration Inhibitory Factor
- Reproductive tract infections research
- Eosinophilic Disorders and Syndromes
- Autoimmune and Inflammatory Disorders Research
- Complement system in diseases
- Venomous Animal Envenomation and Studies
University of Lübeck
2012-2022
Institute of Medical Microbiology and Hygiene
2002-2015
German Center for Infection Research
2015
University Hospital Schleswig-Holstein
2007
Philipps University of Marburg
2003
Friedrich-Alexander-Universität Erlangen-Nürnberg
1993-1998
Armauer Hansen Research Institute
1991-1995
Karolinska Institutet
1986-1987
Hungarian National Blood Transfusion Service
1982-1987
KU Leuven
1986
Macrophages (MF) are the final host cells for multiplication of intracellular parasite Leishmania major (L. major). However, polymorphonuclear neutrophil granulocytes (PMN), not MF, first leukocytes that migrate to site infection and encounter parasites. Our previous studies indicated PMN phagocytose but do kill L. major. Upon with Leishmania, apoptosis human is delayed takes 2 days occur. Infected were found secrete high levels chemokine MIP-1beta, which attracts MF. In this study, we...
Canonical neutrophil antimicrobial effector mechanisms, such as degranulation, production of reactive oxygen species, and release extracellular traps (NETs), can result in severe pathology. Activation neutrophils through immune complexes (ICs) plays a central role the pathogenesis many autoimmune inflammatory diseases. In this study, we report that immobilized ICs (iICs), which are hallmarks several diseases, induce NETs from primary human neutrophils. The iIC-induced NET formation was found...
Neutrophils act as the first line of defense against invading pathogens. Although traditionally considered in context their antimicrobial effector functions, importance tumor-associated neutrophils (TANs) development cancer has become increasingly clear during last decade. With regard to high plasticity, were shown acquire an anti-tumorigenic N1 or a pro-tumorigenic N2 phenotype. Despite urgent need get comprehensive understanding interaction TANs with tumor microenvironment, most studies...
Neutrophil extracellular traps (NETs) consist of decondensed nuclear chromatin that is associated with proteins and are released by neutrophils during an inflammatory response. Released NETs able to capture pathogens, prevent their dissemination potentially kill them via antimicrobial peptides the chromatin. In addition functions, have also been shown exert immunomodulatory effects activation differentiation macrophages, dendritic cells T cells. However, effect on neutrophil functions poorly...
Type 2 nitric oxide synthase (NOS2) is required for the Th1-dependent healing of infections with intracellular microbes, including Leishmania major. Here, we demonstrate expression and define function NOS2 during innate response to L. At day 1 infection, genetic deletion or functional inactivation abolished IFNγ natural killer cell response, increased TGFβ, caused parasite spreading from skin lymph node spleen, liver, bone marrow, lung. Induction was dependent on IFNα/β. Neutralization...
Abstract Macrophages are the major target cell population of obligate intracellular parasites Leishmania. Although polymorphonuclear neutrophil granulocytes (PMN) able to internalize Leishmania promastigotes, these cells have not been considered date as host for parasites, primarily due their short life span. In vitro coincubation experiments were conducted investigate whether can modify spontaneous apoptosis human PMN. Coincubation PMN with promastigotes resulted in a significant decrease...
The formation of neutrophil extracellular traps (NETs) depends on the generation reactive oxygen species (ROS). Previous studies revealed that both NADPH oxidase and myeloperoxidase (MPO) are required for NET release. However, contribution various ROS as well role mitochondria-derived has not been addressed so far. In present study we aimed to investigate in a systematic comprehensive manner ROS-generating pathways PMA-induced By using specific inhibitors, oxidase- superoxide dismutase (SOD)...
The obligate intracellular pathogen Leishmania major survives and multiplies in professional phagocytes. evasion strategy to circumvent killing by host phagocytes establish a productive infection is poorly understood. Here we report that the virulent inoculum of promastigotes contains high ratio annexin A5-binding apoptotic parasites. This subpopulation parasites characterized round body shape, swollen kinetoplast, nuclear condensation, lack multiplication represents dying or already dead...
ABSTRACT The role of polymorphonuclear neutrophil granulocytes (PMN) in defense against the intracellular parasite Leishmania is poorly understood. In present study, interaction human PMN with major promastigotes was investigated vitro. presence fresh serum, about 50% phagocytosed parasites within 10 min and uptake led to activation, resulting killing most ingested parasites. Heat inactivation serum markedly reduced rate early phagocytosis, suggesting a complement components . However, over...
Lipoteichoic acid (LTA) is a major component of the cell membrane gram-positive bacteria. Although LTA has become increasingly recognized as an immunomodulator, its effect on polymorphonuclear neutrophil granulocytes (PMN) still not clear. The interaction between and PMN, however, particular importance, PMN are first leukocytes that migrate to site infection encounter bacterial pathogens. In present study, highly purified human with endotoxin-free from Staphylococcus aureus was investigated....
Abstract The obligate intracellular bacterial pathogen Chlamydia pneumoniae (Cp) is responsible for a range of human diseases, including acute respiratory infection. Although experimental intratracheal infection with Cp results in massive recruitment neutrophil granulocytes (polymorphonuclear neutrophils (PMN)), the role these cells defense against unclear. In this study interactions PMN were investigated. vitro coincubation experiments showed that able to internalize an opsonin-independent...
Abstract We investigated the early spread of Leishmania major in various mouse strains. In BALB/c mice, which are extremely vulnerable to L. infection, parasites disseminated within 10‐24 h from site subcutaneous footpad infection popliteal lymph node, spleen, lung, liver and bone marrow. Application recombinant (r)IL‐12 prior prevented dissemination into visceral organs animals healed infection. three strains tested, C57BL/6, CBA/J C3H/HeJ, all resistant remained localized draining LN for 3...
Recent data from our laboratory suggest that neutrophil granulocytes (polymorphonuclear leukocytes [PMN]) can serve as host cells for Leishmania major in the early phase of infection. In line with these findings, an influx PMN to infected tissues was shown by others be associated susceptibility infection L. major. The mechanisms underlying initial recruitment site is poorly understood. present study we investigated whether influence migration. Supernatants promastigotes were tested their...
Neutrophil granulocytes are rapidly recruited from the bloodstream to site of acute inflammation where they die in large numbers. Because release toxic substances dead neutrophils can propagate inflammatory response leading tissue destruction, clearance dying has a critical function resolution response. Apoptotic phagocytosed primarily by macrophages, provided these cells present adequate However, macrophages rare at sites inflammation, whereas number be extremely high. In current study,...
Autoantibody-mediated diseases are clinically heterogeneous and often fail conventional therapeutic strategies. Gene expression profiling has helped to identify new molecular pathways in these diseases, although their potential as treatment targets largely remains be functionally validated. Based on weighted gene co-expression network analysis, we determined the transcriptional experimental epidermolysis bullosa acquisita (EBA), a paradigm of an antibody-mediated organ-specific autoimmune...
The inflammatory microenvironment is commonly characterized by extracellular acidosis (pH < 7.35). Sensitivity to pH, CO2 or bicarbonate concentrations allows neutrophils react changes in their environment and detect inflamed areas the tissue. One important antimicrobial effector mechanism production of neutrophil traps (NETs), which are released during a programmed reactive oxygen species (ROS)-dependent cell death, so-called NETosis. Although several functions have been analyzed under...
Neutrophil extracellular traps (NETs) have been suggested to play a pathophysiological role in several autoimmune diseases. Since NET-formation response biological and chemical stimuli is mostly ROS dependent, theory any substance that inhibits or scavenges could prevent ROS-dependent NET release. Therefore, the present comprehensive study, antioxidative substances were assessed for their capacity inhibit formation of primary human neutrophils vitro . We show flavonoids (−)-epicatechin,...
The abundance of macro phages in localized cutaneous leishmaniasis (LCL) and diffuse (DCL) lesions differences the composition T cell subsets indicate involvement cell-specific chemotaxis processes. expression macrophage chemoattractant protein (MCP)-1, inflammatory (MIP)-1α -1β, RANTES (regulated on activation, normal expressed secreted), I-309, interleukin-8 were investigated patients with LCL or DCL. In LCL, high levels MCP-1 moderate MIP-1α detected. DCL, was significantly lower...