A5051677576- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Reproductive System and Pregnancy
- HIV Research and Treatment
- IL-33, ST2, and ILC Pathways
- Immune cells in cancer
- Immune Response and Inflammation
- Cancer Cells and Metastasis
- Liver physiology and pathology
- 3D Printing in Biomedical Research
- Cell Image Analysis Techniques
- Immunotherapy and Immune Responses
- Liver Diseases and Immunity
- Hematopoietic Stem Cell Transplantation
- Virus-based gene therapy research
Leibniz Institute of Virology (LIV)
2016-2024
Leibniz Association
2022
German Center for Infection Research
2019
Kupffer cells (KCs) are localized in liver sinusoids but extend pseudopods to parenchymal maintain their identity and serve as the body's central bacterial filter. Liver cirrhosis drastically alters vascular architecture, how KCs adapt is unclear. We used a mouse model of fibrosis human tissue examine immune adaptation. Fibrosis forced lose contact with cells, down-regulating "KC identity," which rendered them incapable clearing bacteria. Commensals stimulated recruitment monocytes through...
Although natural killer (NK) cells are recognized for their modulation of immune responses, the mechanisms by which human NK mediate regulation unclear. Here, we report that expression leukocyte antigen (HLA)-DP, a ligand activating cell receptor NKp44, is significantly upregulated on CD8
HIV-1 establishes a pool of latently infected cells early following infection. New therapeutic approaches aiming at diminishing this persisting reservoir by reactivation are currently being developed and tested. However, the kinetics viral mRNA protein production, their respective consequences for phenotypical changes in that might enable immune recognition, remain poorly understood. We adapted novel approach to assess dynamics expression newly on single-cell level flow cytometry. This...
The crosstalk between NK cells and their surrounding environment is enabled through activating inhibitory receptors, which tightly control cell activity. co-inhibitory receptor TIGIT decreases cytotoxicity involved in exhaustion, but has also been associated with liver regeneration, highlighting that the contribution of human intrahepatic CD56 bright regulating tissue homeostasis remains incompletely understood. A targeted single-cell mRNA analysis revealed distinct transcriptional...
For almost two decades, it was thought that HIV-1 selectively downregulated the highly expressed HLA-I molecules HLA-A and HLA-B from cell surface in order to evade cytotoxic-T-cell recognition, while leaving HLA-C HLA-E unaltered. It stipulated infection thereby maintained inhibition of NK cells via inhibitory receptors bind HLA-E. This concept recently revised when a study showed primary strains reduce levels, whereas line-adapted strain NL4-3 lacks this ability. Here, we demonstrate with...
NK cells utilize a large array of receptors to screen their surroundings for aberrant or virus-infected cells. Given the vast diversity expressed on we seek identify involved in recognition HIV-1-infected By combining an unbiased large-scale screening approach with functional assay, TRAIL be associated cell degranulation against target Further investigating underlying mechanisms, demonstrate that is able elicit multiple effector functions human independent receptor-mediated induction...
Background & AimsUlcerative colitis (UC) is characterized by severe inflammation and destruction of the intestinal epithelium, associated with specific risk single nucleotide polymorphisms in HLA class II. Given recently discovered interactions between subsets HLA-DP molecules activating natural killer (NK) cell receptor NKp44, genetic associations UC haplotypes their functional implications were investigated.MethodsHLA-DP haplotype association analyses performed (UC: n = 13,927; control:...
Natural Killer (NK) cells were initially described as part of the innate immune system and characterized by their ability to lyse malignant virus-infected cells. The cytolytic function NK is tightly controlled activating inhibitory receptors expressed on cell surface. Ligands that interact with a variety NK-cell include human leukocyte antigen (HLA) molecules, regulation HLA class I molecules well established. Earlier studies also suggested role II in regulating activity; yet, interactions...
Objective Primary sclerosing cholangitis (PSC) is characterised by bile duct strictures and progressive liver disease, eventually requiring transplantation. Although the pathogenesis of PSC remains incompletely understood, strong associations with HLA-class II haplotypes have been described. As specific HLA-DP molecules can bind activating NK-cell receptor NKp44, we investigated role HLA-DP/NKp44-interactions in PSC. Design Liver tissue, intrahepatic peripheral blood lymphocytes individuals...
NK cells play a pivotal role in viral immunity, utilizing large array of activating and inhibitory receptors to identify eliminate virus-infected cells. Killer-cell immunoglobulin-like (KIRs) represent highly polymorphic receptor family, regulating cell activity determining the ability recognize target Human leukocyte antigen (HLA) class I molecules serve as primary ligand for KIRs. Herein, HLA-C stands out being dominant majority Accumulating evidence indicated that interactions between its...
KIR3DS1 + NK cells execute enhanced killing of adenovirus-infected cells, providing protection against severe infection in immunocompromised hosts.
Antiviral NK cell activity is regulated through the interaction of activating and inhibitory receptors with their ligands on infected cells. HLA class I molecules serve as for most killer immunoglobulin-like (KIRs), but no receptor KIR2DL5 have been identified to date. Using a receptor/ligand screening approach, we observed strong binding or II molecules, confirmed that binds poliovirus (PVR, CD155). Functional studies using primary human cells revealed significantly decreased degranulation...
Macrophages play central roles in inflammatory reactions and initiation of immune responses during infections. More than 80% total tissue macrophages are described to be located the liver as liver-derived macrophages, also named Kupffer cells (KCs). While studies mice have established a role liver-resident KCs regulating inflammation, their phenotype function not well characterized humans. Comparing paired human peripheral blood samples, we observed significant differences distribution...
Abstract Organoids have emerged as a powerful technology to investigate human development, model diseases and for drug discovery. However, analysis tools rapidly reproducibly quantify organoid parameters from microscopy images are lacking. We developed deep-learning based generalized annotation tool (GOAT) using instance segmentation with pixel-level identification of organoids advanced features. Using multicentric dataset, including multiple systems (e.g. liver, intestine, tumor, lung), we...