Peter F Zipfel

Peter F Zipfel
Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute | HKI · Department of Infection Biology

Professor

About

707
Publications
55,313
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
26,531
Citations
Additional affiliations
January 2012 - present
January 2010 - present
January 2009 - December 2011
Lund University

Publications

Publications (707)
Article
The Gram positive human pathogen Staphylococcus aureus causes a spectrum of human diseases including pneumonia, tissue and skin infections, endocarditis, pneumonia and sepsis. The increasing number of resistant bacteria and the threat of methicillin resistant S. aureus (MRSA) urge for the need to develop new antibacterial compounds. A prerequisite...
Article
Full-text available
The renal disorder C3 glomerulopathy with dense deposit disease (C3G-DDD) pattern results from complement dysfunction and primarily affects children and young adults. There is no effective treatment, and patients often progress to end-stage renal failure. A small fraction of C3G-DDD cases linked to factor H or C3 gene mutations as well as autoantib...
Article
Background: A common haplotype in the gene for the regulator of the alternative pathway of complement activation factor H has been linked to individual predisposition to age- related macular degeneration (AMD). Methods: In this study, retinal pigment epithelial (RPE) cells, i.e. immortalized ARPE-19 as well as primary human RPE cells, were inves...
Article
Deficiency of complement factor H-related (CFHR) proteins and CFH autoantibody-positive hemolytic uremic syndrome (DEAP-HUS) represents a unique subgroup of complement-mediated atypical HUS (aHUS). Autoantibodies to the C-terminus of CFH block CFH surface recognition and mimic mutations found in the genetic form of (CFH-mediated) aHUS. CFH autoanti...
Article
Paul Ehrlich was a pioneering Immunobiologist and physician who coined the term ‘complement’ in the year 1899. He was a leading visionary scientist who worked in the late 19th and early 20th centuries in Berlin and Frankfurt. He received numerous awards and honors for his substantial contributions to immunobiology and medicine, including the identi...
Preprint
Streptococcus pneumoniae is a Gram-positive opportunistic pathogen that can colonize the upper respiratory tract. It is a leading cause of a wide range of infectious diseases, including community-acquired pneumonia, meningitis, otitis media and bacteraemia. Pneumococcal infections cause 1–2 million deaths per year, most of which occur in developing...
Article
C3 glomerulopathy (C3GP) is caused by persisting activity of the complement system and characterized by glomerular deposition of C3, demonstrated by immunohistochemistry. Also in most of the other forms of glomerulonephritis (GN) deposition of complement factors occurs. However, here the significance and predominant activation pathways are less cle...
Article
Full-text available
Since the re-classification of membranoproliferative glomerulonephritis the new disease entity C3 glomerulopathy is diagnosed if C3 deposition is clearly dominant over immunoglobulins in immunohistochemistry or immunofluorescence. Although this new definition is more orientated at the pathophysiology as mediated by activity of the alternative compl...
Article
Full-text available
Sialic acids as the terminal caps of the cellular glycocalyx play an essential role in self-recognition and were shown to modulate complement processes via interaction between α2,3-linked sialic acids and complement factor H. Previously, it was suggested that low molecular weight α2,8-linked polysialic acid (polySia avDP20) interferes with compleme...
Article
Full-text available
The complement system constitutes the innate defense against pathogens. Its dysregulation leads to diseases and is a critical determinant in many viral infections, e.g., COVID-19. Factor H (FH) is the main regulator of the alternative pathway of complement activation and could be a therapy to restore homeostasis. However, recombinant FH is not avai...
Article
Full-text available
Defective complement activation has been associated with various types of kidney disease. This led to the hypothesis that specific urine complement fragments may be associated with kidney disease etiologies, and disease progression may be reflected by changes in these complement fragments. We investigated the occurrence of complement fragments in u...
Article
Full-text available
Atherosclerotic cardiovascular disease (ACVD) is a lipid-driven inflammatory disease and one of the leading causes of death worldwide. Lipid deposits in the arterial wall lead to the formation of plaques that involve lipid oxidation, cellular necrosis, and complement activation, resulting in inflammation and thrombosis. The present study found that...
Article
Full-text available
Staphylococcus aureus is an opportunistic pathogen that can cause life-threatening infections, particularly in immunocompromised individuals. The high-level virulence of S. aureus largely relies on its diverse and variable collection of virulence factors and immune-evasion proteins, including the six serine protease-like proteins SplA-SplF. Spl pro...
Article
Full-text available
Complement is an evolutionarily conserved system which is important in the defense against microorganisms and also in the elimination of modified or necrotic elements of the body. Complement is activated in a cascade type manner and activation and all steps of cascade progression are tightly controlled and regulatory interleaved with many processes...
Preprint
Full-text available
The complement system constitutes the innate defense against pathogens. Its dysregulation leads to diseases and is a critical determinant in many viral infections, e.g.COVID-19. Factor H (FH) is the main regulator of the alternative pathway of complement activation and could be a therapy to restore homeostasis. However, recombinant FH is not availa...
Article
Full-text available
We show that the intraerythrocytic stages of the malaria parasite Plasmodium falciparum bind plasminogen and mediate its conversion into plasmin to inactivate parasite‐bound C3b. This complement evasion mechanism counteracts terminal complex formation and hence promotes parasite survival in human blood.
Article
Full-text available
The PspC and Hic proteins of Streptococcuspneumoniae are some of the most variable microbial immune evasion proteins identified to date. Due to structural similarities and conserved binding profiles, it was assumed for a long time that these pneumococcal surface proteins represent a protein family comprised of eleven subgroups. Recently, however, t...
Article
Full-text available
Complement, as a central immune surveillance system, can be activated within seconds upon stimulation, thereby displaying multiple immune effector functions. However, in pathologic scenarios (like in tumor progression), activated complement can both display protective effects to control tumor development and passively promotes the tumor growth. Cli...
Article
Full-text available
Factor H‐related protein 1 (FHR‐1) is a member of the factor H protein family, which is involved in regulating innate immune complement reactions. Genetic modification of the encoding gene, CFHR1 on human chromosome 1, is involved in diseases such as age‐related macular degeneration, C3‐glomerulopathy, and atypical hemolytic uremic syndrome, indica...
Article
ZUSAMMENFASSUNG Im Verlauf einer Infektion mit dem SARS-CoV-2-Virus kommt es nicht selten zu einer akuten Niereninsuffizienz. Bei einem Teil der Patienten liegt bereits ein vorbestehender chronischer Schaden vor, zumeist aufgrund einer hypertensiven Schädigung, zum Teil auch aufgrund einer diabetischen Glomerulosklerose. Wie es zur akuten Komponent...
Article
C3 glomerulonephritis (C3GN) is a rare but severe form of kidney disease caused by fluid-phase dysregulation of the alternative complement pathway. Causative mutations in complement regulating genes as well as auto-immune forms of C3GN have been described. However, therapy and prognosis in individual patients remain a matter of debate and long-term...
Article
Full-text available
The complement system is part of the innate immune system and plays an important role in the host defense against infectious pathogens. One of the main effects is the opsonization of foreign invaders and subsequent uptake by phagocytosis. Due to the continuous default basal level of active complement molecules, a tight regulation is required to pro...
Preprint
Full-text available
PspC and Hic proteins of Streptococcus pneumoniae are some of the most variable microbial immune evasion proteins identified to date. Due to structural similarities and conserved binding profiles it was assumed over a long time that these pneumococcal surface proteins represent a protein family, comprising eleven subgroups. Recently, however, by ev...
Article
Full-text available
The complement system, originally classified as part of innate immunity, is a tightly self-regulated system consisting of liquid phase, cell surface, and intracellular proteins. In the blood circulation, the complement system, platelets, coagulation system, and fibrinolysis system form a close and complex network. They activate and regulate each ot...
Article
Full-text available
Extracellular vesicles have an important function in cellular communication. Here, we show that human and mouse monocytes release TGF-β1-transporting vesicles in response to the pathogenic fungus Candida albicans. Soluble β-glucan from C. albicans binds to complement receptor 3 (CR3, also known as CD11b/CD18) on monocytes and induces the release of...
Article
Full-text available
Significance Dysregulation of the alternative complement pathway due to impaired binding of complement factor H (CFH) to self-ligands or altered self-ligands (e.g. malondialdehyde [MDA]-modified molecules) involved in homeostasis can promote the development of complement-related diseases, such as age-related macular degeneration (AMD). We identifie...
Article
Full-text available
Invasive fungal infections caused by the mold Aspergillus fumigatus are a growing concern in the clinic due to the increasing use of immunosuppressive therapies and increasing antifungal drug resistance. These infections result in high rates of mortality, as treatment and diagnostic options remain limited. In healthy individuals, neutrophilic granu...
Article
Sequence and copy number variations in the human CFHR-Factor H gene cluster comprising the complement genes CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, and Factor H are linked to the human kidney diseases atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy. Distinct genetic and chromosomal alterations, deletions, or duplications generate hybrid...
Article
Full-text available
Borrelia (B.) mayonii sp. nov. has recently been reported as a novel human pathogenic spirochete causing Lyme disease (LD) in North America. Previous data reveal a higher spirochaetemia in the blood compared to patients infected by LD spirochetes belonging to the B. burgdorferi sensu lato complex, suggesting that this novel genospecies must exploit...
Article
Full-text available
The opportunistic fungal pathogen Aspergillus fumigatus can cause severe infections, particularly in immunocompromised individuals. Upon infection, A. fumigatus faces the powerful and directly acting immune defense of the human host. The mechanisms on how A. fumigatus evades innate immune attack and complement are still poorly understood. Here, we...
Article
Full-text available
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, CD66a) is a receptor for Candida albicans. It is crucial for the immune response of intestinal epithelial cells to this opportunistic pathogen. Moreover, CEACAM1 is of importance for the mucosal colonization by different bacterial pathogens. We therefore studied the influence of th...
Article
Full-text available
Defective complement action is a cause of several human glomerular diseases including atypical hemolytic uremic syndrome (aHUS), anti-neutrophil cytoplasmic antibody mediated vasculitis (ANCA), C3 glomerulopathy, IgA nephropathy, immune complex membranoproliferative glomerulonephritis, ischemic reperfusion injury, lupus nephritis, membranous nephro...
Article
Full-text available
Persistent inflammation is a hallmark of many human diseases, including anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and atherosclerosis. Here, we describe a dominant trigger of inflammation: human serum factor H-related protein FHR1. In vitro, this protein selectively binds to necrotic cells via its N-terminus; in addition, it...
Article
Full-text available
C3 glomerulopathy (C3G) is a severe kidney disease, which is caused by defective regulation of the alternative complement pathway. Disease pathogenesis is heterogeneous and is caused by both autoimmune and genetic factors. Here we characterized IgG autoantibodies derived from 33 patients with autoimmune C3 glomerulopathy. Serum antibodies from all...
Article
Full-text available
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Preprint
Full-text available
Polymorphonuclear granulocytes (PMNs) are indispensable for controlling life-threatening fungal infections. In addition to various effector mechanisms, PMNs also produce extracellular vesicles (EVs). Their contribution to antifungal defense has remained unexplored. We reveal that the clinically important human pathogenic fungus Aspergillus fumigatu...
Article
Full-text available
Apolipoprotein-E (ApoE) has been implicated in Alzheimer’s disease, atherosclerosis, and other unresolvable inflammatory conditions but a common mechanism of action remains elusive. We found in ApoE-deficient mice that oxidized lipids activated the classical complement cascade (CCC), resulting in leukocyte infiltration of the choroid plexus (ChP)....
Article
Full-text available
In the version of this article originally published, a sentence was erroneously included in the author contributions, and information regarding second shared authorship was missing from the author contributions. The following should not have been included in the author contributions: “C.W. and A.J.R.H. supervised the work presented in Figs. 1, 2, 5...
Article
The human complement system is an important part of the immune system responsible for lysis and elimination of invading microorganisms and apoptotic body cells. Improper activation of the system due to deficiency, mutations or autoantibodies of complement regulators, mainly factor H (FH) and FH-related proteins (FHR), causes severe kidney and eye d...
Article
Full-text available
Molecular mimicry is the formation of specific molecules by microbial pathogens to avoid recognition and attack by the immune system of the host. Several pathogenic Ascomycota and Zygomycota show such a behaviour by utilizing human complement factor H to hide in the blood stream. We call this type of mimicry molecular crypsis. Such a crypsis can re...
Data
Opsonization states and relevant complement factor concentrations without the scaling factor accounting for spatial effects. (PDF)
Data
Opsonization states and relevant complement factor concentrations with higher heparan sulfate concentration and lower Pra1 concentration on the surfaces. (PDF)
Data
Example dynamics assuming no inflow of C3 and FH. (PDF)
Data
Complement protein concentrations used in the model. (PDF)
Data
Scaling factor for the affinity of surface derived nascent C3b to the originating surface. (PDF)
Data
Diagram of all reactions occurring in the C. albicans model. (PDF)
Data
Example dynamics assuming inflow of C3 and FH limited only by blood flow. (PDF)
Data
Opsonization states and relevant complement factor concentrations assuming unlimited inflow of C3 and FH. (PDF)
Data
Surface area distributions and erythrocyte count distribution used for sampling. (PDF)
Data
Opsonization states and relevant complement factor concentrations assuming inflow of C3 and FH limited only by blood flow. (PDF)
Data
Opsonization states and relevant complement factor concentrations assuming no inflow of C3 and FH. (PDF)
Data
Kinetic rate constants used in the model. (PDF)