Toll-like receptor 4 and CD11b expressed on microglia coordinate eradication of Candida albicans cerebral mycosis.

The fungal pathogen Candida albicans is linked to chronic brain diseases such as Alzheimer's disease (AD), but the molecular basis of brain anti-Candida immunity remains unknown. We show that C. albicans enters the mouse brain from the blood and induces two neuroimmune sensing mechanisms involving secreted aspartic proteinases (Saps) and candidalysin.

"We've got to get out"-Strategies of human pathogenic fungi to escape from phagocytes.

Human fungal pathogens are a deadly and underappreciated risk to global health that most severely affect immunocompromised individuals. A virulence attribute shared by some of the most clinically relevant fungal species is their ability to survive inside macrophages and escape from these immune cells. In this review, we discuss the mechanisms behind intracellular survival and elaborate how escape is mediated by lytic and non-lytic pathways as well as strategies to induce programmed host cell death.

Candida albicans induces neutrophil extracellular traps and leucotoxic hypercitrullination via candidalysin.

The peptide toxin candidalysin, secreted by Candida albicans hyphae, promotes stimulation of neutrophil extracellular traps (NETs). However, candidalysin alone triggers a distinct mechanism for NET-like structures (NLS), which are more compact and less fibrous than canonical NETs. Candidalysin activates NADPH oxidase and calcium influx, with both processes contributing to morphological changes in neutrophils resulting in NLS formation.

A phylogenetic approach to explore the conidial surface-associated proteome and its role in pathogenesis.

, an important pulmonary fungal pathogen causing several diseases collectively called aspergillosis, relies on asexual spores (conidia) for initiating host infection. Here, we used a phylogenomic approach to compare proteins in the conidial surface of , two closely related non-pathogenic species, and , and the cryptic pathogen . After identifying 62 proteins uniquely expressed on the conidial surface, we assessed null mutants for 42 genes encoding conidial proteins.

Selection of cross-reactive T cells by commensal and food-derived yeasts drives cytotoxic T1 cell responses in Crohn's disease.

Aberrant CD4 T cell reactivity against intestinal microorganisms is considered to drive mucosal inflammation in inflammatory bowel diseases. The disease-relevant microbial species and the corresponding microorganism-specific, pathogenic T cell phenotypes remain largely unknown. In the present study, we identified common gut commensal and food-derived yeasts, as direct activators of altered CD4 T cell reactions in patients with Crohn's disease (CD).

Inability to work following COVID-19 vaccination-a relevant aspect for future booster vaccinations.

Objectives: COVID-19 vaccination is a key prevention strategy to reduce the spread and severity of SARS-CoV-2 infections. However, vaccine-related inability to work among healthcare workers (HCWs) could overstrain healthcare systems.

Study Design: The study presented was conducted as part of the prospective CoVacSer cohort study.

Ncs2* mediates in vivo virulence of pathogenic yeast through sulphur modification of cytoplasmic transfer RNA.

Fungal pathogens threaten ecosystems and human health. Understanding the molecular basis of their virulence is key to develop new treatment strategies. Here, we characterize NCS2*, a point mutation identified in a clinical baker's yeast isolate.

Tolerance of repeated toxic injuries of murine livers is associated with steatosis and inflammation.

The human liver has a remarkable capacity to regenerate and thus compensate over decades for fibrosis caused by toxic chemicals, drugs, alcohol, or malnutrition. To date, no protective mechanisms have been identified that help the liver tolerate these repeated injuries. In this study, we revealed dysregulation of lipid metabolism and mild inflammation as protective mechanisms by studying longitudinal multi-omic measurements of liver fibrosis induced by repeated CCl injections in mice (n = 45).

BMP-2 (and partially GDF-5) coating significantly accelerates and augments bone formation close to hydroxyapatite/tricalcium-phosphate/brushite implant cylinders for tibial bone defects in senile, osteopenic sheep.

Bilateral defects (diameter 8 mm) in the medial tibial head of senile, osteopenic female sheep (n = 48; 9.63 ± 0.10 years; mean ± SEM) were treated with hydroxyapatite (HA)/beta-tricalcium phosphate (β-TCP)/dicalcium phosphate dihydrate (DCPD; brushite) cylinders coated with BMP-2 (25 or 250 micrograms) or growth differentiation factor (GDF)-5 (125 or 1250 micrograms; left side); cylinders without BMP served as controls (right side).

Increased plasma level of terminal complement complex in AMD patients: potential functional consequences for RPE cells.

Purpose: Polymorphisms in complement genes are risk-associated for age-related macular degeneration (AMD). Functional analysis revealed a common deficiency to control the alternative complement pathway by risk-associated gene polymorphisms. Thus, we investigated the levels of terminal complement complex (TCC) in the plasma of wet AMD patients with defined genotypes and the impact of the complement activation of their plasma on second-messenger signaling, gene expression, and cytokine/chemokine secretion in retinal pigment epithelium (RPE) cells.

Pathogen-specific innate immune response patterns are distinctly affected by genetic diversity.

Innate immune responses vary by pathogen and host genetics. We analyze quantitative trait loci (eQTLs) and transcriptomes of monocytes from 215 individuals stimulated by fungal, Gram-negative or Gram-positive bacterial pathogens. We identify conserved monocyte responses to bacterial pathogens and a distinct antifungal response.

The relationship between mental health, sleep quality and the immunogenicity of COVID-19 vaccinations.

Sleep modulates the immune response, and sleep loss can reduce vaccine immunogenicity; vice versa, immune responses impact sleep. We aimed to investigate the influence of mental health and sleep quality on the immunogenicity of COVID-19 vaccinations and, conversely, of COVID-19 vaccinations on sleep quality. The prospective CoVacSer study monitored mental health, sleep quality and Anti-SARS-CoV-2-Spike IgG titres in a cohort of 1082 healthcare workers from 29 September 2021 to 19 December 2022.

"Under Pressure" - How fungi evade, exploit, and modulate cells of the innate immune system.

The human immune system uses an arsenal of effector mechanisms to prevent and counteract infections. Yet, some fungal species are extremely successful as human pathogens, which can be attributed to a wide variety of strategies by which these fungi evade, exploit, and modulate the immune system. These fungal pathogens normally are either harmless commensals or environmental fungi.

Tuning the corona-core ratio of polyplex micelles for selective oligonucleotide delivery to hepatocytes or hepatic immune cells.

Targeted delivery of oligonucleotides or small molecular drugs to hepatocytes, the liver's parenchymal cells, is challenging without targeting moiety due to the highly efficient mononuclear phagocyte system (MPS) of the liver. The MPS comprises Kupffer cells and specialized sinusoidal endothelial cells, efficiently clearing nanocarriers regardless of their size and surface properties. Physiologically, this non-parenchymal shield protects hepatocytes; however, these local barriers must be overcome for drug delivery.

Immunogenicity and safety of coadministration of COVID-19 and influenza vaccination.

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Candidalysin Is the Hemolytic Factor of .

produces an important virulence factor, the hypha-associated -derived secreted peptide toxin candidalysin, which is crucial for the establishment of mucosal and systemic infections. has also long been known to be hemolytic, yet the hemolytic factor has not been clearly identified. Here, we show that candidalysin is the hemolytic factor of .

Influencing factors of anti-SARS-CoV-2-spike-IgG antibody titers in healthcare workers: A cross-section study.

Against the background of the current COVID-19 infection dynamics with its rapid spread of SARS-CoV-2 variants of concern (VOC), the immunity and the vaccine prevention of healthcare workers (HCWs) against SARS-CoV-2 continues to be of high importance. This observational cross-section study assesses factors influencing the level of anti-SARS-CoV-2-spike IgG after SARS-CoV-2 infection or vaccination. One thousand seven hundred and fifty HCWs were recruited meeting the following inclusion criteria: age ≥18 years, PCR-confirmed SARS-CoV-2 infection convalescence and/or at least one dose of COVID-19 vaccination.

Acceptance of Different Self-sampling Methods for Semiweekly SARS-CoV-2 Testing in Asymptomatic Children and Childcare Workers at German Day Care Centers: A Nonrandomized Controlled Trial.

Importance: Closure of day care centers (DCCs) to contain the COVID-19 pandemic has been associated with negative effects on children's health and well-being.

Objective: To investigate the acceptance of self-sampling methods for continuous SARS-CoV-2 surveillance among asymptomatic children and childcare workers (CCWs) in DCCs.

Design, Setting, And Participants: This nonrandomized pilot study included children and CCWs at 9 DCCs in Wuerzburg, Germany, from May to July 2021.

Synthesis and evaluation of novel furanones as biofilm inhibitors in opportunistic human pathogens.

Diseases caused by biofilm-forming pathogens are becoming increasingly prevalent and represent a major threat to human health. This trend has prompted a search for novel inhibitors of microbial biofilms which could, for example, be used to potentiate existing antibiotics. Naturally-occurring, halogenated furanones isolated from marine algae have proven to be effective biofilm inhibitors in several bacterial species.

Virus variant-specific clinical performance of SARS coronavirus two rapid antigen tests in point-of-care use, from November 2020 to January 2022.

Objectives: Antigen rapid diagnostic tests (RDTs) for SARS coronavirus 2 (SARS-CoV-2) are quick, widely available, and inexpensive. Consequently, RDTs have been established as an alternative and additional diagnostic strategy to quantitative reverse transcription polymerase chain reaction (RT-qPCR). However, reliable clinical and large-scale performance data specific to a SARS-CoV-2 virus variant of concern (VOC) are limited, especially for the Omicron VOC.