A5102932319- Research on Leishmaniasis Studies
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Trypanosoma species research and implications
- Immune Cell Function and Interaction
- Urticaria and Related Conditions
- Immune Response and Inflammation
- Eosinophilic Disorders and Syndromes
- Toxin Mechanisms and Immunotoxins
- Parasites and Host Interactions
- Immune cells in cancer
- T-cell and Retrovirus Studies
- Autoimmune and Inflammatory Disorders Research
- Cell Adhesion Molecules Research
- Transgenic Plants and Applications
- Chemokine receptors and signaling
- Cellular Mechanics and Interactions
- Mass Spectrometry Techniques and Applications
- Parasitic Infections and Diagnostics
- CAR-T cell therapy research
- vaccines and immunoinformatics approaches
- Antimicrobial Peptides and Activities
- Cytomegalovirus and herpesvirus research
- Lung Cancer Research Studies
- RNA Interference and Gene Delivery
University of Regensburg
2014-2024
Leibniz Association
2024
Leibniz Institute for Immunotherapy
2022-2024
University Hospital Regensburg
2018
Heinrich Heine University Düsseldorf
2009
Bernhard Nocht Institute for Tropical Medicine
2006-2009
Hôtel-Dieu de Paris
2009
Assistance Publique – Hôpitaux de Paris
2009
Queen's University Belfast
2009
Friedrich-Alexander-Universität Erlangen-Nürnberg
2002-2004
Murine regulatory T (Treg) cells in tissues promote tissue homeostasis and regeneration. We sought to identify features that characterize human Treg with these functions healthy tissues. Single-cell chromatin accessibility profiles of murine defined a conserved, microbiota-independent tissue-repair signature prevailing footprint the transcription factor BATF. This signature, combined gene expression profiling TCR fate mapping, identified population tissue-like peripheral blood expressed...
CD8 T lymphocytes are classically viewed as cytotoxic cells. Whether human cells can, in parallel, induce a tissue regeneration program is poorly understood. Here, antigen-specific assay systems revealed that not only mediated cytotoxicity but also promoted remodeling. Activated could produce the epidermal growth factor receptor (EGFR)-ligand amphiregulin (AREG) and sensitize epithelial for enhanced potential. Blocking EGFR or effector cytokines IFN-γ TNF inhibit This regenerative tumor...
Abstract The resolution of infections with the protozoan parasite Leishmania major in mice requires a Th1 response that is closely associated expression IL-12, IFN-γ, and inducible NO synthase. Previous Ab neutralization studies or use deficient for both TNF receptors suggested plays only limited role control replication vivo. In this study we demonstrate resistant C57BL/6 (B6.WT) locally infected L. rapidly succumb to progressive visceral leishmaniasis after deletion gene by homologous...
In the early phase of leishmaniasis three types potential antigen-presenting cells, including epidermal Langerhans cells (LC), dermal dendritic (DC) and inflammatory DC, are localized at site infection. Therefore, it has been a central question which cell type is responsible for initiation protective immune response. stage an anti-Leishmania response, detectable Leishmania major antigen was in paracortex draining lymph nodes (LN). Characterization antigen-positive showed that L. co-localized...
TNF and receptor type 2 (TNFR2) have been shown to be important for generation of myeloid-derived suppressor cells (MDSC). In order analyze whether how TNFR2 passes the effect on, myeloid from TNFR2-deficient mice were compared respective wild-type mice. Primary showed reduced production NO IL-6 which was attributable CD11b(+) CD11c(-) Ly6C(+) Ly6G(-) immature monocytic MDSC. MDSC isolated bone marrow less suppressive T cell proliferation WT-derived These differences on between two mouse...
Abstract Mutations and activation of the PI3K signaling pathway in breast cancer cells have been linked to brain metastases. However, here we describe that some metastases samples protein expression components is restricted metastatic microenvironment. In contrast therapeutic effects inhibition on cells, reaction microenvironment less understood. Therefore aimed quantify activity metastasis investigate central nervous system (CNS) First, systematically metastases, performed a prospective...
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...
Humoral immunity is maintained by long-lived plasma cells, constitutively secreting antibodies, and nonsecreting resting memory B cells that are rapidly reactivated upon antigen encounter. The activation requirements for particularly the role of T helper unclear. To analyze mice were immunized with human cytomegalovirus, a complex herpesvirus, tick-born encephalitis virus, simple flavivirus. cell populations devoid Ig-secreting adoptively transferred into cell–deficient RAG-1−/− mice....
Abstract The biological role of Langerin+ dendritic cells (DCs) such as Langerhans and a subset dermal DCs (dDCs) in adaptive immunity against cutaneous pathogens remains enigmatic. Thus, we analyzed the impact T cell-mediated toward Leishmania major parasites Lang-DTR mouse model that allows conditional diphtheria toxin (DT)-induced ablation vivo. For first time, infection experiments with DT-treated mice revealed proliferation L. major-specific CD8+ is significantly reduced during early...
Abstract Hypoxia-inducible factor-1α (HIF-1α), which accumulates in mammalian host organisms during infection, supports the defense against microbial pathogens. However, whether and to what extent HIF-1α expressed by myeloid cells contributes innate immune response Leishmania major parasites is unknown. We observed that Leishmania-infected humans L. major–infected C57BL/6 mice exhibited substantial amounts of acute cutaneous lesions. In vitro, was required for leishmanicidal activity...
We recently demonstrated that monocyte chemotactic protein-1 (MCP-1) is strongly expressed in lesions of patients with self-healing localized cutaneous leishmaniasis (LCL) whereas it scarce those chronic diffuse (DCL). This finding indicated MCP-1 may contribute to the healing process. In present study, we analyzed capacity trigger leishmanicidal activities. The results show directly stimulates elimination intracellular Leishmania parasites by human monocytes, a potential correlates...
Abstract Dendritic cells (DCs) generated from bone marrow (BM) precursor of C57BL/6 (B6.WT) mice and cultured in the presence granulocyte macrophage-colony stimulating factor differentiate to mature BM-DCs spontaneously. These DCs are characterized by high levels major histocompatibility complex (MHC) class II, CD40, CD86 on their surface. To analyze involvement tumor necrosis (TNF) related cytokine lymphotoxin (LT)α DC maturation, we studied development BM B6.TNF−/−, B6.LTα−/−,...
Abstract Gene gun immunization, i.e., bombardment of skin with DNA-coated particles, is an efficient method for the administration DNA vaccines. Direct transfection APC or cross-presentation exogenous Ag acquired from transfected nonimmune cells enables MHC-I-restricted activation CD8+ T cells. Additionally, MHC-II-restricted presentation activates CD4+ Th Being principal in epidermis, Langerhans (LC) seem ideal candidates to accomplish these functions. However, dependence on LC gene...
The transmembrane glycoprotein CD83 has been described as a specific maturation marker for dendritic cells and several lines of evidence suggest that regulates thymic T cell well peripheral activation. Here we show the first time is involved also in regulation B function. up-regulated on activated vivo, specifically draining lymph nodes Leishmania major-infected mice. ubiquitous transgenic (Tg) expression interferes with Leishmania-specific cell-dependent cell-independent antibody...
Leishmania pathogenesis is primarily studied using the disease-inducing promastigote stage of major. Despite many efforts, all attempts so far have failed to culture disease-relevant multiplying amastigote L. Here, we established a stably growing axenic major system that was characterized genetically, morphologically, and by stage-specific DsRed protein expression. We found parasite disease development in resistant C57BL/6 mice. Human neutrophils, as first host cells for promastigotes, do...
Tuberculosis patients and mice infected with live Mycobacterium tuberculosis accumulate high numbers of myeloid-derived suppressor cells (MDSCs). Here, we hypothesized that dead M. vaccines also may induce MDSCs could impair the efficacy vaccination. We found repeated injections (heat-killed in incomplete Freund's adjuvant, such as Montanide) but not single or control without strongly expanded CD11b+ myeloid spleen, leading to T cell suppression proliferation killing ex vivo. Dead...
Organoids are three-dimensional (3D) structures that can be derived from stem cells or adult tissue progenitor and exhibit an extraordinary ability to autonomously organize resemble the cellular composition architectural integrity of specific segments. This feature makes them a useful tool for analyzing therapeutical relevant aspects, including organ development, wound healing, immune disorders drug discovery. Most organoid models do not contain mimic neighboring tissue’s microenvironment,...
Background Leishmania (L.) species are the causative agent of leishmaniasis. Due to lack efficient vaccine candidates, drug therapies only option deal with cutaneous Unfortunately, chemotherapeutic interventions show high toxicity in addition an increased risk dissemination drug-resistant parasites. An appropriate laboratory animal based model is still missing which allows testing new strategies context human immune cells vivo. Methodology/Principal Findings Humanized mice were infected...