Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

26.05.2017

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections. If, however, this bacterium overcomes the external barrier such as skin or the mucosa, thus, invading the body, it can cause infections.


Methicillin-resistant Staphylococcus aureus (MRSA) (mustard-coloured) engulfed by a red coloured white blood cells (neutrophil granulocyte)

National Institute of Allergy and Infectious Diseases (NIAID)

Staphylococcus aureus is responsible for a variety of infections that occur in hospitals or care facilities. Some S. aureus strains develop resistances against multiple antibiotics. These so-called MRSAs (multi-resistant S. aureus) cause infections difficult to treat.

So far, all attempts to develop a protective vaccine against S. aureus have failed despite promising results in animal models. One reason might be that the mechanisms of the human immune response against this pathogen are so far not sufficiently understood. In healthy adults, specific immune cells of the adaptive immune system – so-called T-cells – can specifically recognise S. aureus.

There are different T-cells, distinguishable by their surface proteins, which are required for binding to antigen-presenting cells. It was already known that so-called CD4-postive (CD4 protein bearing) T-helper cells can be formed during the immune response against S. aureus. However, these CD4-positive T-cells are not effective against bacteria loacted within cells.

The situation is different for CD8-positive T-cells. They recognise fragments of bacteria which have been processed within the cell and are presented on the surface and provoke the killing of these infected cells. Researchers at the PEI under the supervision of Priv.-Doz. Dr Isabelle Bekeredjian-Ding (MD), head of Division Microbiology demonstrated for the first time that specific CD8-positive T-cells against S. aureus are also formed by the immune system.

However, when examining this T-cell subtype, the researchers realised that when getting into contact with S. aureus, these cells produced substances that did not support the elimination of the pathogen. Instead, the type of released messenger substances assumes that they contribute to immune tolerance against the bacterium by influencing so-called regulatory T-cells and type-2 helper cells. Such influenced regulatory T-cells can prevent or inhibit the activation of the immune response, thus controlling tolerance of the immune system. That way, they can prevent the elimination of the bacterium.

In addition, the PEI researchers were able to show that S. aureus mediated the production of factor G-CSF (Granulocyte-Colony Stimulating Factor) which is, among other things, released during inflammations of the body and inhibits inflammatory T-cell responses. However, the researchers did not only detect T-cell responses that inhibited immunity but also T-cell responses to S. aureus, which were able to start inflammatory processes and could in principle induce the clearance of the pathogenic agent. However, their ratio compared with regulatory T-cells was so low that their effect was negligible.

Dr Bekeredjian-Ding and colleagues were able to show now how this ratio can be shifted in favour of a stronger immune response against S. aureus: The proinflammatory T-cell response could be enhanced by adding immune-active S. aureus components, so-called antigens, which were formed by delivery of messenger RNA (mRNA) of the pathogen into certain immune cells. The use of mRNA produced in the laboratory as a source of antigen is already a well-established method of treatment to induce T-cell responses in tumour therapy to kill infected cells. "Our results show that , in fact, an immune memory against Staphylococcus aureus does exist. We consider it as possible that mRNA-containing vaccines can be used to alter T-cell responses against these pathogens in the body and to increase the portion of protective T-cells", explained Dr Bekeredjian-Ding when presenting the results.

Original Publication

Uebele J, Stein C, Nguyen MT, Schneider A, Kleinert F, Tichá O, Bierbaum G, Götz F, Bekeredjian-Ding I (2017): Antigen delivery to dendritic cells shapes human CD4+ and CD8+ T cell memory responses to Staphylococcus aureus.
PLOS Pathog May 25 [Epub ahead of print].

Weitere Informationen:

http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006387

Dr. Susanne Stöcker | idw - Informationsdienst Wissenschaft
Further information:
http://www.pei.de/

More articles from Life Sciences:

nachricht Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo

nachricht Research reveals how order first appears in liquid crystals
23.05.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Research reveals how order first appears in liquid crystals

23.05.2018 | Life Sciences

Space-like gravity weakens biochemical signals in muscle formation

23.05.2018 | Life Sciences

NIST puts the optical microscope under the microscope to achieve atomic accuracy

23.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>