Biology subjects

Stecher, B.

Publications and source records attributed to Stecher, B..

21 records · Page 2Linked to original sources

bioRxiv2020

Helicobacter hepaticus as disease driver in a novel CD40-mediated model of colitis

Gut microbiota and the immune system are in constant exchange, which shapes both, host immunity and microbial communities. Here, improper immune regulation can cause inflammatory bowel disease (IBD) and colitis. Antibody therapies blocking signaling through the CD40 - CD40L axis showed promising results as these molecules have been described to be deregulated in certain IBD patients. To better understand the mechanism, we used transgenic DC-LMP1/CD40 animals, which lack intestinal CD103+ dendritic cells (DCs) and therefore cannot induce regulatory T (iTreg) cells due to a constitutive CD40-signal in CD11c+ cells. These mice rapidly develop spontaneous fatal colitis with an increase of inflammatory IL-17+IFN-{gamma}+ Th17/Th1 and IFN-{gamma}+ Th1 cells. In the present study we analyzed the impact of the microbiota on disease development and detected elevated IgA- and IgG-levels in sera from DC-LMP1/CD40 animals. Their serum antibodies specifically bound intestinal bacteria and we identified a 60 kDa chaperonin GroEL (Hsp60) from Helicobacter hepaticus (Hh) as the main specific antigen targeted in absence of iTregs. When rederived to a different Hh-free SPF-microbiota, mice showed few signs of disease without fatalities, but upon recolonization of mice with Hh we found rapid disease onset and the generation of inflammatory Th17/Th1 and Th1 cells in the colon. Thus, the present work identifies a major bacterial antigen and highlights the impact of specific microorganisms on modulating the host immune response and its role on disease onset, progression and outcome in this colitis model.

immunology↗

bioRxiv2019

The spatial heterogeneity of the gut limits bacteriophage predation leading to the coexistence of antagonist populations of bacteria and their viruses

Bacteria and their viruses, bacteriophages (phages), are the most abundant components of the mammalian gut microbiota where these two entities coexist over time. The ecological dynamics underlying the coexistence between these two antagonistic populations in the gut are unknown. We challenged a murine synthetic bacterial community with a set of virulent phages, to study the factors allowing phages-bacteria coexistence in the gut. We found that coexistence was neither dependent on an arms race between bacteria and phages, nor on the ability of phages to extend host range. Instead, our data suggest that some phage-inaccessible sites in the mucosa of the ileum serve as a spatial refuge for bacteria, which from there disseminate in the gut lumen. Luminal phages amplify by infecting luminal bacteria maintaining phage throughout the gut. We conclude that the heterogeneous distribution of microbes in the gut contributes to the long-term coexistence of phages with phage-susceptible bacteria. This observation could explain the persistence in the human gut of intestinal phages, such as the crAssphage, as well as the low efficiency of oral phage therapy against enteric pathogens in animal models and clinical trials.

microbiology↗

bioRxiv2017

Local interactions lead to spatially correlated gene expression levels in bacterial groups.

Many bacteria live in spatially structured assemblies where the microenvironment of a cell is shaped by the activities of its neighbors. Bacteria regulate their gene expression based on the inferred state of the environment. This raises the question whether the phenotypes of neighboring cells can become correlated through interactions via the shared microenvironment. Here, we addressed this question by following gene expression dynamics in Escherichia coli microcolonies. We observed strong spatial correlations in the expression dynamics for pathways involved in toxin production, SOS-stress response, and metabolism. These correlations can partly be explained by a combination of shared lineage history and spatial gradients in the colony. Interestingly, we also found evidence for cell-cell interactions in SOS-stress response, methionine biosynthesis and overall metabolic activity. Together our data suggests that intercellular feedbacks can couple the phenotypes of neighboring cells, raising the question whether gene-regulatory networks have evolved to spatially organize biological functions.

microbiology↗