Community Research and Development Information Service - CORDIS

H2020

MYCO TRAPS — Result In Brief

Project ID: 700088
Funded under: H2020-EU.1.3.2.
Country: United Kingdom
Domain: Health

New in vivo models for studying and preventing bacterial infection

The MYCO TRAPS project developed new in vivo models to investigate how cells defend themselves against pathogenic microbes.
New in vivo models for studying and preventing bacterial infection
Cell-autonomous immunity refers to the capacity of cells to independently defend themselves against infections. Part of innate immunity, it is a first line of host defence against microbial invasion.

The first and essential step in cell-autonomous host defence is pathogen recognition, which contributes to the detection and precise location of a pathogen by the host cell. Recent research has shown that the components of the cellular cytoskeleton, the complex network of filaments and tubules that define the shape and strength of the cell, also play a major role in cell-autonomous immunity by promoting bacterial sensing and executing antibacterial functions.

The aim of the EU-funded (Marie Skłodowska-Curie Actions Individual Fellowships) MYCO TRAPS project was to discover roles for the cytoskeleton in cell-autonomous immunity to invasive bacterial pathogens, such as Shigella (important human pathogen, responsible for bacillary dysentery) and Mycobacterium marinum (bacterium closely related to M. tuberculosis, used to model tuberculosis in zebrafish). The research was accomplished using high-resolution microscopy techniques and state-of-the-art cell biology tools. “We were able to study Shigella interactions with the cytoskeleton and to investigate the in vivo role of these interactions in cellular immunity,” says Dr Mostowy, the project coordinator of MYCO TRAPS.

A key link between bacterial infection and inflammation

The first part of the project involved the generation of appropriate zebrafish (Danio rerio, a freshwater fish) models required for monitoring bacterial infection. “The main difficulty we encountered was the lack of available tools to visualise cytoskeleton rearrangements in vivo using zebrafish upon bacterial infection,” highlights Dr Mostowy.

The development of mutant and transgenic lines enabled the discovery of a previously unknown mechanism by which septins, a poorly understood component of the cytoskeleton, control inflammation during Shigella infection in vivo.

MYCO TRAPS also helped to discover that emergency production of the main white blood cells used for bacterial infection, granulocytes, can boost innate immune defence against a secondary infection. This highlights the zebrafish as an important animal model to study ‘trained innate immunity’.

New tools for combating infectious diseases

MYCO TRAPS has generated five transgenic in vivo models (septin KO zebrafish lines) that can be used to study susceptibility to infection. “The understanding of trained innate immunity can aid the development of therapies against bacterial infection, whereas the investigation of septins responsible for cellular immunity can elucidate novel mechanisms of host defence,” concludes Dr Mostowy.

Keywords

MYCO TRAPS, model, Shigella, Mycobacterium marinum, innate immunity, cell autonomous immunity, septins, bacterial infection
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