Dietary fiber pectin alters the gut microbiota and diminishes the inflammatory immune responses in an experimental peach allergy mouse model.

Since therapeutic options are limited the utilization of prebiotics is suggested to prevent food allergies (FAs). Using an experimental peach allergy model we explored the effect of dietary fiber pectin, a high-methoxyl heteropolysaccharide, on the manifestation of FA. CBA/J mice were sensitized, subsequently orally boosted and provoked with peach peel extract.

Regulatory workshop on challenge strain development and GMP manufacture - A stakeholder meeting report.

Within the Innovative Health Initiative (IHI) Inno4Vac CHIMICHURRI project, a regulatory workshop was organised on the development and manufacture of challenge agent strains for Controlled Human Infection Model (CHIM) studies. Developers are often uncertain about which GMP requirements or regulatory guidelines apply but should be guided by the 2022 technical white paper "Considerations on the Principles of Development and Manufacturing Qualities of Challenge Agents for Use in Human Infection Models" (published by hVIVO, Wellcome Trust, HIC-Vac consortium members). Where those recommendations cannot be met, regulators advise following the "Principles of GMP" until definitive guidelines are available.

B cell-mediated CD4 T-cell costimulation via CD86 exacerbates pro-inflammatory cytokine production during autoimmune intestinal inflammation.

Dysregulated B cell responses have been described in inflammatory bowel disease (IBD) patients; however, the role of B cells in IBD pathology remained incompletely understood. We here provide evidence for the detrimental role of activated B cells during the onset of autoimmune intestinal inflammation. Using Wiskott-Aldrich Syndrome interacting protein deficient (Wipf1) mice as a mouse model of chronic colitis, we identified clusters of differentiation (CD)86 expression on activated B cells as a crucial factor exacerbating pro-inflammatory cytokine production of intestinal CD4 T cells.

Analysis of Transfusion-Transmitted Bacterial Infections according to German Hemovigilance Data (2011-2020).

Introduction: Following the first assessment of the effects of safety measures taken against transfusion-transmitted bacterial infections (TTBI), the Paul-Ehrlich-Institut (PEI) decided to newly analyze risk minimization measures (RMM) using German hemovigilance data from 2011 to 2020, focusing on blood components, recipients, and bacterial strains.

Materials And Methods: The PEI assessed the imputability of all reported serious adverse reactions (SAR) relying mainly on microbiological test results. Reporting rates (RR) of suspected, confirmed, and fatal confirmed TTBI were calculated and compared to the previous reporting 10-year period (2001-2010) using Poisson regression to estimate RR ratios (RRR).

NOX2 Deficiency Permits Sustained Survival of in Macrophages and Contributes to Severity of Infection.

Although the crucial role of professional phagocytes for the clearance of infections is well-established, several studies indicate an adverse role of leukocytes in the dissemination of during infection. Since only little is known about macrophages in this context, we analyzed the role of macrophages, and in particular reactive oxygen species deficiency, for the seeding of metastases. Infection of bone marrow-derived macrophages (BMDM) with revealed that NADPH oxidase 2 (NOX2-) deficient, but not NOX1- or NOX4-deficient, BMDM failed to clear intracellular .

Epitope-specific immunity against Staphylococcus aureus coproporphyrinogen III oxidase.

Staphylococcus aureus represents a serious infectious threat to global public health and a vaccine against S. aureus represents an unmet medical need. We here characterise two S.

Establishment of transfusion-relevant bacteria reference strains for red blood cells.

Background And Objectives: Red blood cell concentrates (RBCC) are susceptible to bacterial contamination despite cold storage. A reliable evaluation of strategies to minimize the risk of RBCC-associated bacterial transmission requires the use of suitable reference bacteria. Already existing Transfusion-Relevant Bacteria Reference Strains (TRBRS) for platelet concentrates fail to grow in RBCC.

Antibiotic Resistance and Mobile Genetic Elements in Extensively Drug-Resistant Sequence Type 147 Recovered from Germany.

Mobile genetic elements (MGEs), especially multidrug-resistance plasmids, are major vehicles for the dissemination of antimicrobial resistance determinants. Herein, we analyse the MGEs in three extensively drug-resistant (XDR) isolates from Germany. Whole genome sequencing (WGS) is performed using Illumina and MinION platforms followed by core-genome multi-locus sequence typing (MLST).

Kinetic Fingerprinting Links Bacteria-Phage Interactions with Emergent Dynamics: Rapid Depletion of Indicates Phage Synergy.

The specific temporal evolution of bacterial and phage population sizes, in particular bacterial depletion and the emergence of a resistant bacterial population, can be seen as a that depends on the manifold interactions of the specific phage-host pair during the course of infection. We have elaborated such a kinetic fingerprint for a human urinary tract isolate and its phage vB_KpnP_Lessing by a modeling approach based on data from co-culture. We found a faster depletion of the initially sensitive bacterial population than expected from simple mass action kinetics.

Microbiological Screening of Platelet Concentrates in Europe.

The risk of transfusion-associated sepsis due to transmission of bacteria is a persistent problem in the transfusion field. Despite numerous interventions to reduce the risk, cases of bacterial sepsis following transfusion are repeatedly being reported. Especially platelet concentrates are highly susceptible to bacterial contaminations due to the growth-promoting storage conditions.

Mitochondrial reactive oxygen species enable proinflammatory signaling through disulfide linkage of NEMO.

A major function of macrophages during infection is initiation of the proinflammatory response, leading to the secretion of cytokines that help to orchestrate the immune response. Here, we identify reactive oxygen species (ROS) as crucial mediators of proinflammatory signaling leading to cytokine secretion in infected macrophages. ROS produced by NADPH oxidases (Noxes), such as Nox2, are key components of the macrophage response to invading pathogens; however, our data show that the ROS that mediated proinflammatory signaling were produced by mitochondria (mtROS).

Contribution of the Immune Response to Phage Therapy.

Therapeutic phages are being employed for vaccination and treatment of cancer and bacterial infections. Their natural immunogenicity triggers intertwined interactions with innate and adaptive immune cells that might influence therapy. Phage- and bactierial-derived pathogen-associated molecular patterns released after bacterial lysis have been proposed to stimulate local innate immune responses, which could promote antitumor immunity or bacterial clearance.

Diversity of mutations in regulatory genes of resistance-nodulation-cell division efflux pumps in association with tigecycline resistance in Acinetobacter baumannii.

Objectives: To investigate the mechanisms of tigecycline resistance in isogenic Acinetobacter baumannii isolate pairs as well as 65 unique clinical A. baumannii isolates obtained during the MagicBullet clinical trial from Greece, Italy and Spain.

Methods: A.

The β Integrin Mac-1 Induces Protective LC3-Associated Phagocytosis of Listeria monocytogenes.

The intracellular pathogen Listeria monocytogenes (L.m.) is targeted by the autophagic machinery, but the molecular mechanisms involved and consequences for anti-listerial immunity remain enigmatic.

Autophagy determines efficiency of liver-directed gene therapy with adeno-associated viral vectors.

Unlabelled: Use of adeno-associated viral (AAV) vectors for liver-directed gene therapy has shown considerable success, particularly in patients with severe hemophilia B. However, the high vector doses required to reach therapeutic levels of transgene expression caused liver inflammation in some patients that selectively destroyed transduced hepatocytes. We hypothesized that such detrimental immune responses can be avoided by enhancing the efficacy of AAV vectors in hepatocytes.

Recent Zika Virus Isolates Induce Premature Differentiation of Neural Progenitors in Human Brain Organoids.

The recent Zika virus (ZIKV) epidemic is associated with microcephaly in newborns. Although the connection between ZIKV and neurodevelopmental defects is widely recognized, the underlying mechanisms are poorly understood. Here we show that two recently isolated strains of ZIKV, an American strain from an infected fetal brain (FB-GWUH-2016) and a closely-related Asian strain (H/PF/2013), productively infect human iPSC-derived brain organoids.

Loss of the interferon-γ-inducible regulatory immunity-related GTPase (IRG), Irgm1, causes activation of effector IRG proteins on lysosomes, damaging lysosomal function and predicting the dramatic susceptibility of Irgm1-deficient mice to infection.

Background: The interferon-γ (IFN-γ)-inducible immunity-related GTPase (IRG), Irgm1, plays an essential role in restraining activation of the IRG pathogen resistance system. However, the loss of Irgm1 in mice also causes a dramatic but unexplained susceptibility phenotype upon infection with a variety of pathogens, including many not normally controlled by the IRG system. This phenotype is associated with lymphopenia, hemopoietic collapse, and death of the mouse.

Montanide ISA 71 VG is Advantageous to Freund's Adjuvant in Immunization Against S. aureus Infection of Mice.

The enormous capacity of Staphylococcus aureus to acquire antibiotic resistance makes it a permanent task to search for and to develop new anti-infectives. One of the possible approaches is the early active immunization of risk patients and animal stocks to prevent S. aureus infections.

On the antibiotic and antifungal activity of pestalone, pestalachloride A, and structurally related compounds.

Pestalone (1) is a prominent marine natural product first isolated by M. Cueto et al. in 2001 from a co-fermentation of a marine fungus with a marine bacterium.

Guidelines for the use and interpretation of assays for monitoring autophagy.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding.

WIPI-1 Positive Autophagosome-Like Vesicles Entrap Pathogenic Staphylococcus aureus for Lysosomal Degradation.

Invading pathogens provoke the autophagic machinery and, in a process termed xenophagy, the host cell survives because autophagy is employed as a safeguard for pathogens that escaped phagosomes. However, some pathogens can manipulate the autophagic pathway and replicate within the niche of generated autophagosome-like vesicles. By automated fluorescence-based high content analyses, we demonstrate that Staphylococcus aureus strains (USA300, HG001, SA113) stimulate autophagy and become entrapped in intracellular PtdIns(3)P-enriched vesicles that are decorated with human WIPI-1, an essential PtdIns(3)P effector of canonical autophagy and membrane protein of both phagophores and autophagosomes.

Complete failure of insulin-transmitted signaling, but not obesity-induced insulin resistance, impairs respiratory chain function in muscle.

The role of mitochondrial dysfunction in the development of insulin resistance and type 2 diabetes remains controversial. In order to specifically define the relationship between insulin receptor (InsR) signaling, insulin resistance, hyperglycemia, hyperlipidemia and mitochondrial function, we analyzed mitochondrial performance of insulin-sensitive, slow-oxidative muscle in four different mouse models. In obese but normoglycemic ob/ob mice as well as in obese but diabetic mice under high-fat diet, mitochondrial performance remained unchanged even though intramyocellular diacylglycerols (DAGs), triacylglycerols (TAGs), and ceramides accumulated.