A5061305237- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Cytomegalovirus and herpesvirus research
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- Fungal Infections and Studies
- Antifungal resistance and susceptibility
- SARS-CoV-2 and COVID-19 Research
- Polysaccharides and Plant Cell Walls
- Invertebrate Immune Response Mechanisms
- COVID-19 Clinical Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Complement system in diseases
- Long-Term Effects of COVID-19
- Immune Response and Inflammation
- Glycosylation and Glycoproteins Research
- Studies on Chitinases and Chitosanases
- Genetics and Neurodevelopmental Disorders
- vaccines and immunoinformatics approaches
- Galectins and Cancer Biology
- Bone and Dental Protein Studies
- Respiratory viral infections research
- Immune cells in cancer
- Connexins and lens biology
University Hospital Augsburg
2021-2024
University of Augsburg
2021
German Center for Infection Research
2015-2021
Institute of Virology of the Slovak Academy of Sciences
2015
University of Cape Town
2006-2012
Mansfield University
2012
Universitätsklinikum Tübingen
2011
University of Tübingen
2008-2010
Institut de Biologie Moléculaire et Cellulaire
2010
University of Würzburg
2003-2009
Recognition of microbial components by germ-line encoded pattern recognition receptors (PRR) initiates immune responses to infectious agents. We and others have proposed that pairs or sets PRR mediate host immunity. One such pair comprises the fungal beta-glucan receptor, Dectin-1, which collaborates through an undefined mechanism with Toll-like receptor 2 (TLR2) induce optimal cytokine in macrophages. show here Dectin-1 signaling spleen tyrosine kinase (Syk) pathway is required for this...
We describe here the first characterization of CLEC9A, a group V C-type lectin-like receptor located in "Dectin-1 cluster" related receptors, which are encoded within natural killer (NK)-gene complex. Expression human CLEC9A is highly restricted peripheral blood, being detected only on BDCA3(+) dendritic cells and small subset CD14(+)CD16(-) monocytes. expressed at cell surface as glycosylated dimer can mediate endocytosis, but not phagocytosis. possesses cytoplasmic immunoreceptor...
Recognition of microbial products by germ-line-encoded PRR initiates immune responses, but how mediate specific host responses to infectious agents is poorly understood. We and others have proposed that specificity achieved collaborative mediated between different PRR. One such example comprises the fungal beta-glucan receptor Dectin-1, which collaborates with TLR induce TNF production. show here Dectin-1 TLR2 are more extensive than first appreciated, result in enhanced IL-23, IL-6 IL-10...
CLEC-2 is a member of the "dectin-1 cluster" C-type lectin-like receptors and was originally thought to be restricted platelets. In this study, we demonstrate that murine also expressed by peripheral blood neutrophils, but only weakly bone marrow or elicited inflammatory neutrophils. On circulating can mediate phagocytosis Ab-coated beads production proinflammatory cytokines, including TNF-alpha, in response ligand, rhodocytin. possesses tyrosine-based cytoplasmic motif similar dectin-1,...
After COVID-19, some patients develop long-term symptoms. Whether such symptoms correlate with immune responses, and how long immunity persists, is not yet clear. This study focused on mild COVID-19 investigated correlations of persistent longevity. Persistent complications, including headache, concentration difficulties loss smell/taste, were reported by 51 83 (61%) participants decreased over time to 28% one year after COVID-19. Specific IgA IgG antibodies detectable in 78% 66%...
Using fluorescent variants of Fas and FasL, we show that membrane FasL form supramolecular clusters are flexible shape, but nevertheless stable persistent. Membrane FasL-induced were formed in caspase-8– or FADD-deficient cells when a cytoplasmic deletion mutant was used suggesting cluster formation is independent the assembly signaling complex downstream activated pathways. In contrast, cross-linked soluble failed to aggregate Fas, still induced aggregation competent full-length Fas....
Superagonistic CD28-specific monoclonal antibodies (CD28SA) are highly effective activators of regulatory T-cells (Treg cells) in rats, but a first-in-man trial the human CD28SA TGN1412 resulted an unexpected cytokine release syndrome. Using novel mouse anti-mouse CD28SA, we re-investigate relationship between Treg activation and systemic release. by was efficient depended on paracrine IL-2 from CD28SA-stimulated conventional T-cells. Systemic levels were innocuous, depletion cells prior to...
C-type lectins are the most diverse and prevalent lectin family in immunity. Particular interest has recently been attracted by lectin-like receptors on NK cells, which appear to regulate activation/inhibitory balance of these controlling cytotoxicity cytokine production. We previously identified a human receptor, closely related both beta-glucan receptor for oxidized-LDL, named MICL (myeloid inhibitory receptor), we had shown using chimeric analysis function as an receptor. Using novel...
Many well-known immune-related C-type lectin-like receptors (CTLRs) such as NKG2D, CD69, and the Ly49 are encoded in natural killer gene complex (NKC). Recently, we characterized orphan NKC CLEC2A encoding for KACL, a further member of human CLEC2 family CTLRs. In contrast to other members AICL, LLT1, KACL expression is mostly restricted skin. Here show that non–disulfide-linked homodimeric surface receptor stimulates cytotoxicity by NK92MI cells. We identified corresponding activating on...
Significance Human adenoviruses encode Early region 3 (E3) proteins that manipulate the host immune response to establish an infection or persist longer. To date, only a few E3 functions from single adenovirus species (C) have been characterized, all of which act directly on infected cells. Here we describe secreted protein is uniquely expressed by D adenoviruses. This targets noninfected leukocytes using cell surface phosphatase as receptor. We provide evidence this interaction suppresses...
Abstract The human NK cell receptor NKp80 stimulates cytotoxicity upon engagement of its genetically linked ligand AICL. However, the mechanisms underlying NKp80-mediated signaling are unknown. In this study, we dissected using line NK92MI. We demonstrated that NKp80, but not mutated at tyrosine 7 (NKp80/Y7F), is phosphorylated. Accordingly, NKp80/Y7F, NKp80/Y30F or NKp80/Y37F, failed to induce cytotoxicity. phosphopeptides comprising hemi-ITAM–like sequence surrounding bound Lck- and...
CD28 and CTLA-4 are the major costimulatory receptors on naive T cells. But it is not clear why monovalent whereas bivalent for their shared ligands CD80/86. We generated constructs by fusing extracellular domains of or CD80 with intracellular CD28. Bivalent were ligated recombinant without TCR coligation. Monovalent ligation did induce responses unless was coligated. By contrast, induced in absence engagement. To extend these findings to primary cells, we used novel superagonistic...
Almost all physiological T cell responses require costimulation-engagement of the clonotypic TCR with MHC/Ag and CD28 by its ligands CD80/86. Whether provides signals that are qualitatively unique or quantitatively amplify signaling is poorly understood. In this study, we use superagonistic Abs, which induce proliferation without coligation, to determine how contributes mitogenic responses. We show but do not activate proximal components TCRzeta Zap-70 kinase. lines lacking signaling, an...
Studies of knockout mice indicate that the glycoprotein CD5, which is expressed on T cells, most thymocytes and a subset B down-regulates TCR- cell receptor (BCR)-mediated signaling. CD5 associated with TCR BCR, phosphorylated cytoplasmic tyrosine residues following antigen ligation. Cross-linking or pervanadate stimulation induces association 120-kDa tyrosine-phosphorylated protein CD5. The proto-oncoprotein c-cbl associates in pervanadate-stimulated thymocytes, reprecipitation analysis...
Abstract CD5 is a glycoprotein expressed on thymocytes, T cells, and subset of B cells. Antibody‐mediated cross‐linking studies or knockout mice implicate as co‐stimulatory negative regulatory molecule. rapidly phosphorylated tyrosine (Y) residues following cell activation. Y429 Y441 occur in an imperfect immunoreceptor tyrosine‐based activation motif (ITAM)‐like sequence. We investigated whether phosphatidylinositol (PI) 3‐kinase, which binds to tyrosine‐phosphorylated ITAM, interacts with...
Mitogenic anti-CD28 antibody stimulates all peripheral T cells to proliferate in the absence of TCR ligation, providing an exception two-signal requirement cell responses. This preferentially recognizes a mobilized signaling-competent form CD28, normally induced following thus unique non-physiological tool dissect CD28-specific signals leading proliferation. The protein kinase C (PKC)theta-NF-kappaB pathway has recently been shown integrate TCR- and CD28-derived co-stimulation. We now...
Adenovirus often causes respiratory infection in immunocompromised patients, but relevant attachment receptors have largely not been defined. We show that the antiviral protein bovine lactoferrin enhances of monocyte-derived dendritic cells (MDDC) by adenovirus species C serotype 2 (2C) isolates. Under same conditions MDDC human( )cytomegalovirus was reduced. Adenoviral prominently enhanced human lactoferrin, and using blood macrophages, suggesting receptor is expressed on MDDC. Infection...
In symptomatic patients with acute Coronavirus disease 2019 (COVID-19), lymphocytopenia is one of the most prominent laboratory findings. However, to date age and gender have not been considered in assessment COVID-19-related cell count alterations. this study, impact COVID-19 as well on a large variety lymphocyte subsets was analyzed 33 compared counts 50 healthy humans. We confirm that total lymphocytes, B, NK, cytotoxic helper T cells are reduced severe COVID-19, tendency observed...