Testicular germ cell tumours (TGCT) are thought to originate from fetal cells that fail differentiate normally, but no animal model for these events has been described. We evaluated the marmoset (Callithrix jacchus) as a by comparing perinatal differentiation with in humans.Immunohistochemical profiling was used investigate (OCT4, NANOG, AP-2gamma, MAGE-A4, VASA, NANOS-1) and proliferation (Ki67) neonatal testes comparison human and, lesser extent, rat.In marmosets humans, of gonocytes into...

Rosetting, the adhesion of Plasmodium falciparum-infected erythrocytes to uninfected erythrocytes, involves clonal variants parasite protein P. falciparum erythrocyte membrane 1 (PfEMP1) and soluble serum factors. While rosetting is a well-known phenotypic marker parasites associated with severe malaria, reason for this association remains unclear, as do molecular details interaction between infected (IE) adhering erythrocytes. Here, we identify first time single factor, abundant protease...

B cells are key pathogenic drivers of chronic inflammation in rheumatoid arthritis (RA). There is limited understanding the relationship between synovial cell subsets and antibody secreting (ASCs). This knowledge crucial for development more targeted B-cell depleting therapies. While CD11c+ double-negative 2 (DN2) have been suggested as an ASC precursor lupus, to date there no proven link two RA. We used both single-cell gene expression BCR sequencing study from patients with established RA,...

Pneumolysin is an important virulence factor of the human pathogen Streptococcus pneumoniae. Sequence analysis ply gene from 121 clinical isolates S. pneumoniae uncovered a number alleles. Twenty-two strains were chosen for further analysis, and 14 protein alleles discovered. Five these had been reported previously, remaining 9 novel. Cell lysates used to determine specific hemolytic activities pneumolysin proteins. Six showed no activity, 16 hemolytic, varying degrees. We report that...

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a common and debilitating chronic illness of unknown aetiology. Chronic infection autoimmune responses have been proposed as two mechanisms that potentially underlie the pathogenesis ME/CFS. To explore these disease hypotheses, we characterised antigen-specific receptors B cells using adaptive immune receptor repertoire sequencing. We compared B-cell (BCR) repertoires 25 patients with mild/moderate ME/CFS, 36 severe 21 healthy...

SUMMARY Despite the overlapping distribution of Schistosoma haematobium and Plasmodium falciparum infections, few studies have investigated early immune responses to both parasites in young children resident areas co-endemic for parasites. This study measures infection levels relates them exposure children. Levels IgM, IgE, IgG4 directed against schistosome cercariae, egg adult worm IgG P. schizonts merozoite surface proteins 1 2 together with cytokines IFN- γ , IL-4, IL-5, IL-10 TNF- α were...

Abstract The cytoplasmic phosphatase, protein tyrosine phosphatase nonreceptor type 22 (PTPN22), is a negative regulator of T cell signaling. Genome-wide association studies have shown that single-nucleotide polymorphisms in PTPN22 confer an increased risk developing multiple autoimmune diseases humans. precise function and how the variant contributes to autoimmunity not well understood. To address this issue, we investigated effect deficiency on disease susceptibility mouse model arthritis....

B cells are critical for promoting autoimmunity and the success of cell depletion therapy in rheumatoid arthritis (RA) confirms their importance driving chronic inflammation. Whilst disease specific autoantibodies useful diagnostically, our understanding pathogenic repertoire remains unclear. Defining it would lead to novel insights curative treatments. To address this, we have undertaken largest study date over 150 RA patients, utilizing next generation sequencing (NGS) analyse up 200,000...

Adoptive immunotherapy with Epstein-Barr virus (EBV)-specific T cells is an effective treatment for relapsed or refractory EBV-induced post-transplant lymphoproliferative disorders (PTLD) overall survival rates of up to 69%. EBV-specific have been conventionally made by repeated stimulation EBV-transformed lymphoblastoid cell lines (LCL), which act as antigen-presenting cells. However, this process expensive, takes many months, and has practical risks associated live virus. We developed a...

Polymorphic parasite antigens are known targets of protective immunity to malaria, but this antigenic variation poses challenges vaccine development. A synthetic MSP-1 Block 2 construct, based on all polymorphic variants found in natural Plasmodium falciparum isolates has been designed, combined with the relatively conserved 1 sequence and expressed E.coli. The Hybrid antigen produced high yield by fed-batch fermentation purified without aid affinity tags resulting a pure extremely...

The chronic autoimmune inflammatory diseases, systemic lupus erythematosus and Sjogren's syndrome, develop when tolerance to apoptotic cells (ACs) is lost. We have previously reported that this maintained by innate-like, IL-10 secreting regulatory B cells. Two questions remained. First, do these belong predominantly a single subset of steady-state second, what their specificity? report here innate-like with markers characteristic for B1a (CD43+veCD19hiCD5+veIgMhiIgDlo) constitute 80% splenic...

Abstract Intermedilysin is a pore‐forming cytolysin belonging to the streptolysin O gene family known as ‘Cholesterol‐binding/dependent cytolysins’ and unique within in that it highly human‐specific. This specificity suggests interaction with component of human cells other than cholesterol, proposed receptor for toxins family. Indeed, intermedilysin showed no significant degree affinity free or liposome‐embedded cholesterol. Characterization undecapeptide mutants revealed this lack...

Summary This study was designed to investigate the relationship between influx of extracellular Ca2+, activation NFκB and synthesis interleukin-8 (IL-8) following exposure human neutrophils subcytolytic concentrations (8·37 41·75 ng/ml) pneumococcal toxin, pneumolysin, as well potential omega-3 polyunsaturated fatty acid, docosahexaenoic antagonize these events. Activation translocation were measured using a radiometric electrophoretic mobility shift assay, while Ca2+ IL-8 determined...

// Graeme Cowan 1, * , Nicola J. Weston-Bell 2, Dean Bryant 2 Anja Seckinger 3 Dirk Hose Niklas Zojer 4 Surinder S. Sahota 1 Institute of Immunology and Infection Research, Centre for Immunity, Evolution, University Edinburgh, UK Tumour Immunogenetics Group, Cancer Sciences Academic Unit, Faculty Medicine, Southampton, Medizinische Klinik V, Universitätsklinikum Heidelberg, Germany Center Oncology Hematology, 1st Department Wilhelminenspital, Vienna, Austria These authors have contributed...

Development of effective malaria vaccines is hampered by the problem producing correctly folded Plasmodium proteins for use as vaccine components. We have investigated a novel ciliate expression system, Tetrahymena thermophila, P. falciparum antigen platform. A synthetic composed N-terminal and C-terminal regions merozoite surface protein-1 (MSP-1) was expressed in thermophila. The recombinant secreted into culture medium purified monoclonal antibody (mAb) affinity chromatography....

The unique species specificity of the bacterial cytolysin intermedilysin is explained by its requirement for human complement regulator CD59 as primary receptor. Binding studies using individual domains mapped CD59-binding site to domain 4 and swap mutants between rabbit (non-intermedilysin-binding) implicated a short sequence (residues 42-59) in binding intermedilysin. We set out map more closely first looked regions homology terminal components that bind CD59, C8 C9. A nine amino acid...

Adaptive Immune Receptor Repertoire Sequencing is a rapidly developing field that has advanced understanding of the role adaptive immune system in health and disease. Numerous tools have been developed to analyse complex data produced by this technique but work compare their accuracy reliability limited. Thorough, systematic assessment performance dependent on ability produce high quality simulated datasets with known ground truth. We AIRRSHIP, flexible fast Python package produces synthetic...

Streptoccocus pneumoniae infection can result in local and systemic diseases such as otitis media, pneumonia meningitis. Sensorineural hearing loss associated with this is mediated by the release of an exotoxin, pneumolysin. The goal present study was to characterize mechanisms pneumolysin toxicity cochlear hair cells vitro. Pneumolysin induced severe damage cells, ranging from stereocilia disorganization total cell loss. Surprisingly, pneumolysin-induced death preferentially targeted inner...

SUMMARY With the current paucity of vaccine targets for parasitic diseases, particularly those in childhood, aim this study was to compare protein expression and immune cross-reactivity between trematodes Schistosoma haematobium, S. bovis Echinostoma caproni hope identifying novel intervention targets. Native adult parasite proteins were separated by 2-dimensional gel electrophoresis identified through electrospray ionisation tandem mass spectrometry produce a reference gel. Proteins from...

The Block 2 region of the merozoite surface protein-1 (MSP-1) Plasmodium falciparum has been identified as a target protective immunity by combination seroepidemiology and parasite population genetics. Immunogenicity studies in small animals Aotus monkeys were used to determine efficacy recombinant antigens derived from this MSP-1 potential vaccine antigen. lemurinus griseimembra immunized three times with antigen monkey-adapted challenge strain, FVO falciparum, using an adjuvant suitable...

Urogenital schistosomiasis, due to Schistosoma haematobium, is endemic in sub-Saharan Africa. Control by targeted treatment with praziquantel but preschool age children are excluded from control programs. Immunological studies on the effect of at this young scarce. In light older individuals showing that alters antischistosome immune responses and bystander antigens, study aims investigate how these would be affected age. Antibody directed against schistosome Plasmodium falciparum crude...

CD4 + αβ T-cells are key mediators of the immune response to a first Plasmodium infection, undergoing extensive activation and splenic expansion during acute phase an infection. However, clonality clonal composition this has not previously been described. Using comparative infection model, we sequenced T-cell receptor repertoires generated over time-course chabaudi We show through repeat replicate experiments, single-cell RNA-seq, analyses independent RNA-seq data, that following - within...