- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Cancer Research and Treatments
- Immune Response and Inflammation
- interferon and immune responses
- Nanoplatforms for cancer theranostics
- Listeria monocytogenes in Food Safety
- Virus-based gene therapy research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Cytokine Signaling Pathways and Interactions
- Mycobacterium research and diagnosis
- Bacteriophages and microbial interactions
- Neutropenia and Cancer Infections
- Orthopedic Infections and Treatments
- Bacterial biofilms and quorum sensing
- Immune cells in cancer
- Glycosylation and Glycoproteins Research
- Escherichia coli research studies
- Salmonella and Campylobacter epidemiology
- Vibrio bacteria research studies
- Pharmacological Effects of Natural Compounds
- Extraction and Separation Processes
- Bacterial Genetics and Biotechnology
Helmholtz Centre for Infection Research
2011-2025
Medizinische Hochschule Hannover
2010-2023
Institute of Immunology
1991-2023
Center for Experimental and Clinical Infection Research
2014-2020
Salk Institute for Biological Studies
1984-2015
Universidade Federal de Mato Grosso do Sul
2015
Center of Molecular Immunology (Cuba)
2006-2012
Paul Ehrlich Institut
2007
University of Duisburg-Essen
2006-2007
University of Ljubljana
2007
Angiogenesis is a hallmark of malignant neoplasias, as the formation new blood vessels required for tumors to acquire oxygen and nutrients essential their continued growth metastasis. However, signaling pathways leading tumor vascularization are not fully understood. Here, using transplantable mouse model, we have demonstrated that endogenous IFN-beta inhibits angiogenesis through repression genes encoding proangiogenic homing factors in tumor-infiltrating neutrophils. We determined...
The importance of tumor associated neutrophils (TANs) in cancer development is the meantime well established. Numerous clinical data document adverse prognostic effects neutrophil infiltration solid tumors. However, certain therapies need functional to be effective, suggesting altered polarization with different outcomes for patients. Therefore, modulation neutrophilic phenotypes represents a potent therapeutic option, but factors mediating are still poorly defined. In this manuscript we...
Abstract Stable expression of Foxp3 in regulatory T cells (Tregs) depends on DNA demethylation at the Treg-specific demethylated region (TSDR), a conserved, CpG-rich within locus. The TSDR is selectively ex vivo Tregs purified from secondary lymphoid organs, but it unclear which stage Treg development takes place. In this study, we show that commitment to stable lineage occurred during early stages murine thymic by engraving lineage-specific epigenetic marks parallel with establishment gene...
Objective The spondyloarthritides (SpA) are a group of rheumatic diseases characterized by ossification and inflammation entheseal tissue, the region where tendon attaches to bone. Interleukin‐23 (IL‐23) is involved in pathogenesis SpA acting on IL‐23 receptor (IL‐23R) expressed enthesis‐resident lymphocytes. Upon binding, CD3+CD4−CD8− tissue‐resident lymphocytes secrete IL‐17A IL‐22, leading inflammation, bone loss, ossification. Knowledge about remains fragmentary, contribution γ/δ T cells...
Antigen-presenting B-lymphoma cells were transfected with the gene encoding immunoglobulin lambda 2 light chain of MOPC315 (lambda 2(315). The is expressed on cell surface transfectants together endogenous heavy chain. present an idiotope 2(315) to class II-restricted T-cell clones. Recognition by T requires processing From these data we conclude that constitutively process and their immunoglobulins. Secretion reuptake was not necessary for presentation. Thus, B bear two types idiotypes...
Type I IFN is a major player in innate and adaptive immune responses. Besides, it involved organogenesis tumor development. Generally, responses are amplified by an autocrine loop with IFN-beta as the priming cytokine. However, due to lack of sensitive detection systems, where how type produced vivo still poorly understood. In this study, we describe luciferase reporter mouse, which allows tracking gene induction vivo. Using reveal strong tissue-specific following infection influenza or La...
We have previously demonstrated that one member of the alpha-tubulin multigene family, termed T alpha 1 in rats, is regulated as a function neuronal growth and regeneration. To elucidate molecular mechanisms responsible for coupling gene expression to morphological differentiation, we isolated gene, fused 1.1 kb 5' flanking region nuclear lacZ reporter generated transgenic mice. Analysis these mice marker was specific CNS PNS, with vivo at embryonic day 13.5 being similar endogenous gene....
Administration of facultative anaerobic bacteria like Salmonella typhimurium, Shigella flexneri, and Escherichia coli to tumor-bearing mice leads a preferential accumulation proliferation the microorganisms within solid tumor. Until now, all known tumor-targeting have shown poor dissemination inside tumors. They accumulate almost exclusively in large necrotic areas spare rim viable tumor cells. Interestingly, bacteria-containing region is separated from cells by barrier host neutrophils that...
Summary Infection of a murine‐spleen dendritic cell line by Listeria monocytogenes was found to induce death through apoptosis. To characterize the bacterial product(s) involved in induction apoptosis, cells were infected with L. EGD strain and several isogenic mutants deficient production individual listerial virulence factors. The ability cellular apoptosis retained all tested, except prfA Δ hly mutants, both which are unable produce listeriolysin. Apoptosis also induced purified...
ABSTRACT La Crosse virus (LACV) is a mosquito-transmitted member of the Bunyaviridae family that causes severe encephalitis in children. For LACV nonstructural protein NSs, previous overexpression studies with mammalian cells had suggested two different functions, namely induction apoptosis and inhibition RNA interference (RNAi). Here, we demonstrate mosquito persistently infected do not undergo mount specific RNAi response. Recombinant viruses either express (rLACV) or lack (rLACVdelNSs)...
ABSTRACT Type I interferon (IFN), which includes the IFN-α and -β subtypes, plays an essential role in host defense against influenza A virus. However, relative contribution of IFN-β remains unresolved. In mice, type IFN is effective viruses only if IFN-induced resistance factor Mx1 present, though most inbred mouse strains, including recently developed IFN-β-deficient bear defective alleles. We therefore generated mice carrying functional alleles (designated Mx-BKO) compared them to either...
Natural killer (NK) cells are sentinel components of the innate response to pathogens, but cell types, pathogen recognition receptors, and cytokines required for their activation in vivo poorly defined. Here, we investigated role plasmacytoid dendritic (pDCs), myeloid DCs (mDCs), Toll-like receptors (TLRs), NK stimulatory induction an protozoan parasite Leishmania infantum. In vitro, pDCs did not endocytose promastigotes nevertheless released interferon (IFN)-α/β interleukin (IL)-12 a...
The chemokine receptor CXCR2 and its ligands CXCL1, CXCL2 CXCL5 play an important role in homing of tumor-associated neutrophils (TANs) into developing tumors. TANs are known to support the development blood vessels growing solid tumors, hence contributing tumor growth. Here, we show that migration is influenced by endogenous interferon-beta (IFN-β) via regulation such chemokines their receptor. We could demonstrate CXCL1 gradients formed tumor-bearing mice, i.e., low level bone marrow (BM)...
Background Toll-like receptors (TLRs) are among the first-line sentinels for immune detection and responsiveness to pathogens. The TLR2 subfamily of TLRs (TLR1, TLR2, TLR6) form heterodimers with each other thus able recognize a broad range components from several microbes such as yeast, Gram-positive bacteria protozoa. Until now, activation by bacterial ligands has long been associated pro-inflammatory cytokines but not type I interferon responses. Methodology/Principal Findings Using...
Aicardi-Goutie `res syndrome (AGS), a hereditary autoimmune disease, clinically and biochemically overlaps with systemic lupus erythematosus (SLE) and, like SLE, is characterized by spontaneous type I interferon (IFN) production.The finding that defects of intracellular nucleases cause AGS led to the concept accumulation nucleic acids triggers inappropriate production IFN autoimmunity.AGS can also be caused SAMHD1, 3 0 exonuclease deoxynucleotide (dNTP) triphosphohydrolase.Human SAMHD1 an...
Metastases are the major cause of death from cancer. Thus, understanding regulation metastatic processes is utmost importance. Here we show that mice with impaired type I IFN signaling (Ifnar1(-/-)) develop more lung metastases in 4T1 mammary and LLC carcinoma model, compared to control mice. In Ifnar1(-/-) mice, higher metastasis load accompanied by massive neutrophil accumulation lungs. Elevated G-CSF levels serum enhanced CXCR2 expression on neutrophils most likely responsible for this...