Biology subjects

Ebner, F.

Publications and source records attributed to Ebner, F..

4 recordsLinked to original sources

bioRxiv2026

Microbial Invasion and Immunosuppression Drives Adenoma Progression in Early Colorectal Cancer Development

Several inherited predispositions to colorectal cancer exist, most notably familial adenomatous polyposis (FAP), which typically involves a germline loss-of-function mutation in one APC allele. A second hit in APC or related loci leads to aberrant Wnt signalling, triggering adenoma formation with near-complete penetrance. Yet, substantial variability in disease onset and severity, even among siblings with identical APC germline mutations, implicates environmental modifiers. Emerging evidence points to the gut microbiome as a critical regulator of adenoma initiation and progression, particularly in early-onset CRC. Here, we show that bacterial invasion is associated with neutrophil immunosuppression, T-cell exclusion and adenoma progression in a porcine model of FAP. Longitudinal mapping of progressing and regressing polyps using single-cell RNA sequencing, spatial transcriptomics and integrated microbiome profiling resolved the cellular and microbial architecture underlying these divergent lesion states. Single-cell RNA-seq identified 35 cell subpopulations and showed that regressing polyps are enriched for central-memory CD4+ T cells, cytotoxic CD8+ T cells and inflammatory neutrophils, whereas progressing polyps contain immunosuppressive/PD-L1-associated neutrophils, regulatory and dysfunctional T cells. Spatial transcriptomics with a custom host panel and targeted bacterial probes linked bacterial-high adenomatous regions to immunosuppressive neutrophil niches and T cell exclusion, while regressing lesions showed predominantly lumen-adjacent bacterial localization and spatially organized immune surveillance. These results provide a spatially resolved map of cellular and microbial organisation in early colorectal polyp progression and regression and reveal a microbiome-driven, neutrophil-mediated mechanism of early tumour progression with implications for CRC interception. Grant support: This study was funded by the German Research Foundation (DFG) through SFB1371 "Microbiome signature" (Project no. 395357507; TF, DS, FE, DH) and by the German Ministry for Research and Education (BMBF) through Mi-EOCRC consortium project (Project no. 01KD2102D; KF and DH).

cancer biology↗

bioRxiv2021

A semisynthetic glycoconjugate provides expanded cross-serotype protection against Streptococcus pneumoniae

Streptococcus pneumoniae infections are the leading cause of child mortality globally. Current vaccines fail to induce a protective immune response towards a conserved part of the pathogen, resulting in new serotypes causing disease. Therefore, new vaccine strategies are urgently needed. Described is a two-pronged approach combining S.pneumoniae proteins, pneumolysin and PspA, with a precisely defined synthetic oligosaccharide, whereby the carrier protein acts as a serotype-independent antigen to provide additional protection. Proof of concept in mice and swine models revealed that the conjugates inhibit colonization of the nasopharynx, decrease the bacterial load and reduce disease severity in the bacteria challenged model. Immunization of piglets provided the first evidence for the immunogenicity and protective potential of synthetic glycoconjugate vaccine in a large animal model. A combination of synthetic oligosaccharides with proteins from the target pathogen opens the path to create broadly cross-protective ("universal") pneumococcal vaccines.

immunology↗

bioRxiv2019

CD4+ Th immunogenicity of the Ascaris spp. secreted products

Ascaris spp. is a major health problem of humans and animals alike, and understanding the immunogenicity of its antigens is required for developing urgently needed vaccines. The parasite-secreted products represent the most relevant, yet highly complex (>250 proteins) antigens of Ascaris spp. as defining the pathogen-host interplay. We applied an in vitro antigen processing system coupled to quantitative proteomics to identify potential CD4+ Th cell epitopes in Ascaris suum-secreted products. This approach restricts the theoretical list of epitopes, based on affinity prediction, by a factor of [~]1200. More importantly, selection of 2 candidate peptides based on experimental evidence demonstrated the presence of epitope-reactive T cells in Ascaris-specific T cell lines generated from healthy human individuals. Thus, this stringent work pipeline identifies a human haplotype-specific T cell epitope of a major human pathogen. The methodology described represents an easily adaptable platform for characterization of highly complex pathogenic antigens and their MHCII-restriction.

immunology↗

bioRxiv2019

A helminth chitinase structurally similar to mammalian chitinase displays immunomodulatory properties

Previously, we reported significant immunomodulatory effects of the entire excretory-secretory (ES) proteins of the first larval stage (L1) of the gastrointestinal nematode Trichuris suis in a rodent model of allergic hyperreactivity. In the present study, we aimed to identify the proteins accounting for the modulatory effects of the T. suis L1 ES proteins and thus studied selected components for their immunomodulatory efficacy in an OVA-induced allergic airway disease model. In particular, an enzymatically active T. suis chitinase mediated amelioration of airway hyperreactivity, primarily associated with suppression of eosinophil recruitment into the lung. The three-dimensional structure of the T. suis chitinase as determined by high-resolution X-ray crystallography revealed significant similarities to mouse acidic mammalian chitinase (AMCase). In addition, the unique ability of T. suis chitinase to form dimers, as well as acidic surface patches within the dimerization region may contribute to the formation of cross-reactive antibodies to the mouse homologs. This hypothesis is supported by the observation that T. suis chitinase treatment induced cross-reactive antibodies to mouse AMCase and chitinase-like protein BRP-39 in the AHR model. In conclusion, a biologically active T. suis chitinase exhibits immunomodulatory properties despite its structural similarity to the mammalian counterpart.\n\nAuthor summaryExperimental immunotherapy via reintroduction of intestinal worms to treat and prevent autoimmune, chronic inflammatory or allergic diseases is being discussed but the underlying mechanisms are still not fully understood. Here, we investigated the immunomodulatory potential of specific proteins of the whipworm Trichuris suis that are secreted very early during larval development. Using a murine model of allergic lung disease, we show that in particular one T. suis protein, functionally characterized as an active chitinase, is reducing the lung inflammation. The T. suis chitinases three-dimensional protein structure revealed remarkable similarities to the hosts chitinase, an enzyme known to play a pivotal role in lung allergy. We also show that treatment with the helminth chitinase induced cross-reactive antibody responses against murine chitinase and chitinase-like proteins, both being inflammatory marker and regulators of type 2 immunity. Thus, our study provides a novel mechanism of immunomodulation by helminth components and may contribute to a better understanding of clinical responses of patients receiving helminthic therapy.

immunology↗