András N. Spaan
A5058449340- Antimicrobial Resistance in Staphylococcus
- SARS-CoV-2 and COVID-19 Research
- Immunodeficiency and Autoimmune Disorders
- Diabetes and associated disorders
- COVID-19 Clinical Research Studies
- Immune Response and Inflammation
- Respiratory viral infections research
- Bacterial biofilms and quorum sensing
- NF-κB Signaling Pathways
- interferon and immune responses
- Immune Cell Function and Interaction
- Lipid Membrane Structure and Behavior
- Bacterial Infections and Vaccines
- Single-cell and spatial transcriptomics
- Kawasaki Disease and Coronary Complications
- Streptococcal Infections and Treatments
- Cell Image Analysis Techniques
- Clostridium difficile and Clostridium perfringens research
- Erythrocyte Function and Pathophysiology
- Biochemical and Structural Characterization
- Ubiquitin and proteasome pathways
- Galectins and Cancer Biology
- Hidradenitis Suppurativa and Treatments
- Advanced Biosensing Techniques and Applications
- T-cell and B-cell Immunology
University Medical Center Utrecht
2014-2025
Utrecht University
2022-2025
Rockefeller University
2018-2024
Inserm
2015-2020
Heidelberg University
2017-2018
University Hospital Heidelberg
2017-2018
École Normale Supérieure de Lyon
2015
Centre International de Recherche en Infectiologie
2015
Université Claude Bernard Lyon 1
2015
Centre National de la Recherche Scientifique
2015
Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 987 patients with life-threatening disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), 13 types IFN-α (36), or both (52) onset critical disease; a few also auto-Abs other three type I IFNs. The neutralize ability corresponding IFNs to block...
Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort 1,202 patients 0.5 99 52.9 with unexplained pneumonia. None the 331 asymptomatically or mildly infected 1.3 102 38.7 tested carry such (p = 3.5 × 10-5). The phenotypes five hemizygous relatives...
Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn IFN-α/β-dependent intrinsic viral diseases. Both types IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria related intramacrophagic pathogens. These have no history severe disease, despite exposure to many viruses, including...
Upon contact with human plasma, bacteria are rapidly recognized by the complement system that labels their surface for uptake and clearance phagocytic cells. Staphylococcus aureus secretes 16 kD Extracellular fibrinogen binding protein (Efb) binds two different plasma proteins using separate domains: Efb N-terminus to fibrinogen, while C-terminus C3. In this study, we show blocks phagocytosis of S. neutrophils. vitro, demonstrate in whole blood. Using a mouse peritonitis model effectively...
Staphylococcus aureus virulence has been associated with the production of phenol soluble modulins (PSM). PSM are known to activate, attract and lyse neutrophils. However, functional characterizations were generally performed in absence human serum. Here, we demonstrate that serum can inhibit all previously-described activities PSM. We observed fully block both cell lysis FPR2 activation show a direct interaction between lipoproteins whole blood. Subsequent analysis using purified high, low,...
The molecular basis of interindividual clinical variability upon infection with Staphylococcus aureus is unclear. We describe patients haploinsufficiency for the linear deubiquitinase OTULIN, encoded by a gene on chromosome 5p. Patients suffer from episodes life-threatening necrosis, typically triggered S. infection. disorder phenocopied in 5p- (Cri-du-Chat) chromosomal deletion syndrome. OTULIN causes an accumulation ubiquitin dermal fibroblasts, but tumor necrosis factor receptor-mediated...
Staphylococcus aureus is well adapted to the human host. Evasion of host phagocyte response critical for successful infection. The staphylococcal bicomponent pore-forming toxins Panton-Valentine leukocidin LukSF-PV (PVL) and γ-hemolysin CB (HlgCB) target phagocytes through interaction with complement receptors C5aR1 C5aR2. Currently, apparent redundancy both cannot be adequately addressed in experimental models infection because mice are resistant PVL HlgCB. molecular basis species...
Autosomal dominant (AD) NFKB1 deficiency is thought to be the most common genetic etiology of variable immunodeficiency (CVID). However, causal link between variants and CVID has not been demonstrated experimentally genetically, there insufficient biochemical characterization enrichment analysis. We show that cotransfection NFKB1-deficient HEK293T cells (lacking both p105 its cleaved form p50) with a κB reporter, NFKB1/p105, homodimerization-defective RELA/p65 mutant results in p50:p65...
Most patients with autosomal dominant hyper-IgE syndrome (AD-HIES) carry rare heterozygous STAT3 variants. Only six of the 135 in-frame variants reported have been experimentally shown to be negative (DN), and it has recently suggested that eight out-of-frame operate by haploinsufficiency. We tested these 143 variants, 7 novel found in HIES patients, other from general population. Strikingly, all 15 were DN via their encoded (1) truncated proteins, (2) neoproteins generated a translation...
High-dimensional cytometry is a powerful technique for deciphering the immunopathological factors common to multiple individuals. However, rational comparisons of batches experiments performed on different occasions or at sites are challenging because batch effects. In this study, we describe integration multibatch datasets (iMUBAC), flexible, scalable, and robust computational framework unsupervised cell-type identification across high-dimensional datasets, even without technical...