A5001635220- Immune Cell Function and Interaction
- Hepatitis C virus research
- T-cell and B-cell Immunology
- HIV Research and Treatment
- Liver Disease Diagnosis and Treatment
- Software Engineering Techniques and Practices
- Reproductive System and Pregnancy
- Liver Diseases and Immunity
- Cytomegalovirus and herpesvirus research
- Glycosylation and Glycoproteins Research
- Immune Response and Inflammation
- IL-33, ST2, and ILC Pathways
- Animal Virus Infections Studies
- Hepatitis B Virus Studies
- Liver physiology and pathology
- Monoclonal and Polyclonal Antibodies Research
- Galectins and Cancer Biology
- Antimicrobial Peptides and Activities
- Immunodeficiency and Autoimmune Disorders
- Software Engineering Research
- Lysosomal Storage Disorders Research
- HIV-related health complications and treatments
- Diabetes and associated disorders
- HIV/AIDS Research and Interventions
- Blood disorders and treatments
Leibniz Institute of Virology (LIV)
2015-2023
Siemens (Germany)
1993-2022
Leibniz Association
2022
Ragon Institute of MGH, MIT and Harvard
2012-2018
University of Bonn
2009-2017
Harvard University
2017
Massachusetts Institute of Technology
2012
University Hospital Bonn
2009-2011
German Sport University Cologne
2011
Hospital Universitario de Valme
2010
Human beta-defensin 3 (hBD3) is a highly charged (+11) cationic host defense peptide, produced by epithelial cells and neutrophils. hBD3 retains antimicrobial activity against broad range of pathogens, including multiresistant Staphylococcus aureus, even under high-salt conditions. Whereas peptides are assumed to act permeabilizing cell membranes, the transcriptional response pattern hBD3-treated staphylococcal resembled that vancomycin-treated (V. Sass, U. Pag, A. Tossi, G. Bierbaum, H....
Natural killer (NK) cells play a role in the early control and natural course of hepatitis C virus (HCV) infection. NK cell function is regulated by multitude receptors, including activating NKp46 receptor. However, reports on are controversial. Therefore, we investigated hepatic recruitment NKp46(+) cells, considering differential surface expression resulting NKp46(High) NKp46(Dim) subsets. Intra- extrahepatic NK-cell subsets from HCV-infected patients were characterized flow cytometry....
Background An isoleucine>methionine mutation at position 148 in the PNPLA3 gene (p.I148M, rs738409) has recently been identified as a susceptibility factor for liver damage steatohepatitis. Here, we studied whether rs738409 polymorphism also affects predisposition to hepatocellular carcinoma (HCC). Methods We compared distributions of genotypes 80 and 81 Caucasian patients with alcoholic hepatitis C virus (HCV)-associated HCC age- sex-matched alcohol-related HCV-related cirrhosis without...
Previously, it was found that a novel class of neutral fucosylated glycosphingolipids (GSLs) is required for male fertility. These lipids contain very long-chain (C26-C32) polyunsaturated (4-6 double bonds) fatty acid residues (VLC-PUFAs). To assess the role these complex GSLs in spermatogenesis, we have now investigated with which testicular cell types are associated. During postnatal development, glycosylated and simple VLC-PUFA sphingolipids were first detectable at day 15, when most...
Background Viruses can evade immune surveillance, but the underlying mechanisms are insufficiently understood. Here, we sought to understand by which natural killer (NK) cells recognize HIV-1-infected and how this virus NK-cell-mediated pressure. Methods Findings Two sequence mutations in p24 Gag associated with presence of specific KIR/HLA combined genotypes were identified HIV-1 clade C viruses from a large cohort infected, untreated individuals South Africa (n = 392), suggesting viral...
Leukocyte adhesion deficiency II has been described in only 2 patients; herein we report extensive investigation of another patient. The physical stigmata were detected during prenatal ultrasonographic investigation. Sialyl-Lewis X (sLex) was absent from the surface polymorphonuclear neutrophils, and cell binding to E- P-selectin severely impaired, causing an immunodeficiency. elevation peripheral neutrophil counts occurred within several days after birth. A severe hypofucosylation...
The binding of insulin-like growth factor II (IGF II) to the mannose 6-phosphate (M6P)/IGF receptor has previously been reported induce activation trimeric Gi2 proteins by functional coupling a 14-amino acid region within cytoplasmic domain (Nishimoto, I., Murayama, Y., Katada, T., Ui, M., and Ogata, E.(1989) J. Biol. Chem. 264, 14029-14038). In present study, we examined further potential G-proteins with human M6P/IGF mutant receptors lacking proposed G-protein activator sequence. IGF...
Chronic hepatitis C virus (HCV) infection is a major risk factor for hepatocellular carcinoma (HCC). HCV proteins core and NS3 can bind to toll-like receptor 2 (TLR2) trigger inflammatory responses. Polymorphisms in the TLR2 gene predispose various forms of malignancy but have not been studied HCV-associated HCC. Here, we investigated whether single nucleotide polymorphisms (SNPs), rs4696480, rs5743708, rs5743704 -196 -174 del/ins polymorphism affect HCC chronic C. The study involved 189 192...
Accumulating evidence suggests an important role for Natural Killer (NK) cells in the control of HIV-1 infection. Recently, it was shown that NK cell-mediated immune pressure can result selection escape mutations. A potential mechanism this cell is HLA class I-presented epitopes allow engagement inhibitory killer immunoglobulin-like receptors (KIRs), notably KIR2DL2. We therefore investigated consequences sequence variations within HLA-Cw*0102-restricted on interaction HLA-Cw*0102 with...
Hepatitis C virus (HCV) coinfection is an increasing health problem in human immunodeficiency virus-positive (HIV+) individuals. However, a considerable proportion of HIV+ patients manage to overcome acute hepatitis (AHC) spontaneously. In the present study, we analyzed role natural killer (NK) cells modulating course AHC patients. Twenty-seven with (self-limited course: n = 10; chronic 17), 12 (CHC), 8 HIV monoinfected individuals, and healthy controls were studied. NK phenotypically by...
Abstract Innate lymphoid cells (ILC), including natural killer (NK) cells, are implicated in host-defense and tissue-growth. However, the composition kinetics of NK intestine during first year life, when infants broadly exposed to exogenous antigens, still unclear. Here we show that CD103 + major ILC population small intestines infants. When compared adult intestinal infant exhibit a robust effector phenotype, characterized by Eomes, perforin granzyme B expression, superior degranulation...
Recently, we showed chronic hepatitis C to be associated with increased expression of HLA-E and identified peptide virus (HCV) core amino acids 35-44 as a ligand for that stabilizes expression, favoring inhibition natural killer cell cytotoxicity. Here describe HLA-E-restricted recognition HCV by CD8(+) T cells. Frequency responses was significantly higher in patients homozygous the HLA-E(R) allele (60% vs 38%; P = .038). Moreover, found allelic variant confers protection against infection...
The function of natural killer (NK) cells is controlled by several activating and inhibitory receptors, including the family killer-immunoglobulin-like receptors (KIRs). One distinctive feature KIRs extensive number various haplotypes generated gene content within KIR locus as well highly polymorphic members family, namely KIR3DL1/S1. Within KIR3DL1/S1 locus, KIR3DS1 represents a conserved allelic variant displays other unique features in comparison to KIR3DL1 allele. present all human...
Systemic chemotherapies for various malignancies have been shown to significantly, yet transiently, decrease numbers of CD4+ T lymphocytes, a major reservoir human immunodeficiency virus type 1 (HIV-1) infection. However, little is known about the impact cytoreductive chemotherapy on HIV-1 dynamics, persistence, and immune responses.We investigated changes in peripheral T-cell-associated DNA RNA levels, lymphocyte activation, viral population structure, virus-specific responses longitudinal...
Inflammation in early human immunodeficiency virus type 1 (HIV-1) disease progression is not well characterized. Ninety patients with untreated primary HIV-1 infection were studied to determine associations of inflammatory proteins progression. High plasma tumor necrosis factor α (TNF-α) levels (≥8.5 pg/mL) significantly associated an increased viral load set point and shorter times reaching a CD4+ T-cell count <500 cells/mm3 initiating antiretroviral therapy. The risk the group high TNF-α...
Objective: The aim of this study was to assess the consequence sequence variations in HLA-C*03:04-presented HIV-1 p24 Gag epitopes on binding inhibitory natural killer (NK) cell receptor KIR2DL2 HLA-C*03:04. Design: may possibly evade recognition by KIR+ NK cells through selection variants that interfere with interactions immunoglobulin-like receptors (KIRs) and their target ligands infected cells. is an binds a family HLA-C ligands. Here, we investigated whether encodes for...
NK cells expressing self-inhibitory receptors display increased functionality compared to lacking those receptors. The acquisition of functional competence in these particular NK-cell subsets is termed education. Little known about the underlying mechanisms that lead differences between educated and uneducated cells. An increasing number studies suggest cellular metabolism a determinant immune cell functions. Thus, alterations metabolic pathways may play role process Here, we glycolytic...
Apoptosis importantly contributes to loss of CD4+ T-cells in HIV infection, and modification their apoptosis may explain why HIV/HCV (hepatitis C virus)-co-infected patients are more likely die from liver-related causes, although the effects HCV on infection remain unclear. In present study, we studied a cross-sectional serial analysis spontaneous ex vivo T-cell HIV/HCV-co-infected HIV-mono-infected before after HAART (highly active antiretroviral therapy). peripheral blood was measured by...