Scientists at the University of Liverpool have discovered a new and important function of a toxin produced by disease-causing bacteria that could have significant implications for future vaccine design.
Streptococcus pneumoniae (the pneumococcus) is a major cause of life-threatening invasive diseases such as pneumonia, septicaemia and meningitis, and is responsible for more than one million deaths every year.
Key to its disease-causing success is the action of a potent toxin called pneumolysin, which works by creating 'holes' in the membranes of human cells, and either killing them directly or causing significant tissue damage.
Until now, scientists believed that the effects of pneumolysin resulted purely from the binding of the toxin to cholesterol in host cell membranes.
A new study published in Nature Microbiology, however, shows that pneumolysin can also bind directly to a host cell receptor on specialised immune cells to suppress the immune response.
The study was a collaboration between the Bacterial Pathogenesis and Immunity Group at the University's Institute of Infection and Global Health and the Department of Microbiology, Tumour and Cell Biology at the Karolinska Institute in Stockholm.
Using specialised in vitro experiments in human cells and in vivo studies in mice, the team has shown that pneumolysin can bind directly to a host cell receptor called Mannose Receptor C type-1 (MRC-1) on immune cells, including macrophages and dendritic cells, causing them to reduce their production of molecules that promote inflammation and protective immunity. The bacteria can then survive more easily in the airways, as inflammation and immune cell activity is suppressed.
Professor Aras Kadioglu, who led the study in Liverpool said: "This is really a key moment in our understanding of how the pneumococcus causes disease.
First of all, because it breaks a long-standing dogma that pneumolysin can only bind to cholesterol, indeed the identification of a host receptor for pneumolysin has been the holy grail in the field for many decades, and secondly, because it changes our understanding of how the pneumococcus uses its toxin to manipulate and alter our immune response to its advantage. I am very excited by the potential of these new findings."
Dr Daniel Neill who is a joint first author, added: "Understanding how bacteria are able to promote infection via toxin production will help scientists to develop new ways of combatting serious infectious diseases. Several vaccines in development contain detoxified pneumolysin and it is important that we further explore how the newly-described receptor-binding activity might influence the immune responses induced by such vaccination."
Nicola Frost | EurekAlert!
Researchers find trigger that turns strep infections into flesh-eating disease
19.02.2019 | Houston Methodist
Loss of identity in immune cells explained
18.02.2019 | Technische Universität München
Up to now, OLEDs have been used exclusively as a novel lighting technology for use in luminaires and lamps. However, flexible organic technology can offer much more: as an active lighting surface, it can be combined with a wide variety of materials, not just to modify but to revolutionize the functionality and design of countless existing products. To exemplify this, the Fraunhofer FEP together with the company EMDE development of light GmbH will be presenting hybrid flexible OLEDs integrated into textile designs within the EU-funded project PI-SCALE for the first time at LOPEC (March 19-21, 2019 in Munich, Germany) as examples of some of the many possible applications.
The Fraunhofer FEP, a provider of research and development services in the field of organic electronics, has long been involved in the development of...
For the first time, an international team of scientists based in Regensburg, Germany, has recorded the orbitals of single molecules in different charge states in a novel type of microscopy. The research findings are published under the title “Mapping orbital changes upon electron transfer with tunneling microscopy on insulators” in the prestigious journal “Nature”.
The building blocks of matter surrounding us are atoms and molecules. The properties of that matter, however, are often not set by these building blocks...
Scientists at the University of Konstanz identify fierce competition between the human immune system and bacterial pathogens
Cell biologists from the University of Konstanz shed light on a recent evolutionary process in the human immune system and publish their findings in the...
Laser physicists have taken snapshots of carbon molecules C₆₀ showing how they transform in intense infrared light
When carbon molecules C₆₀ are exposed to an intense infrared light, they change their ball-like structure to a more elongated version. This has now been...
The so-called Abelian sandpile model has been studied by scientists for more than 30 years to better understand a physical phenomenon called self-organized...
11.02.2019 | Event News
30.01.2019 | Event News
16.01.2019 | Event News
20.02.2019 | Life Sciences
20.02.2019 | Medical Engineering
20.02.2019 | Power and Electrical Engineering