Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How friendly bacteria avoids immune attack to live happily in the gut

02.09.2008
For a long time scientists have been puzzled by the fact that the immune system in the gut is capable of fighting toxic bacterial infection while staying, at the same time, tolerant to its resident “friendly” bacteria.

But an article now published in the journal Cell Host & Microbe1 is starting to open the door to this mystery by revealing how a recently discovered gene - pims – is activated by the gut immune response against friendly bacteria to rapidly suppress it, effectively creating tolerance to the gut microbiota.

In the same way pims is also shown to control the magnitude of immune responses against toxic bacteria by suppressing immuno-reactivity when a certain activation threshold is achieved, assuring, in this way, that the response stays restricted to the infection site and is proportional to the extent of the infection. These results suggest that the balance tolerance/immuno-reaction in the gut is achieved through self-regulatory cycles where suppression by negative regulators, such as pims, is triggered as soon as a specific threshold of immuno activation is reached.

This work has implications in the understanding of diseases in which the normal gut immune response is disrupted - such as Crohn's disease and ulcerative colitis – but, potentially, also in oral tolerance. In fact, oral tolerance vaccines - in which the molecule we want immuno-tolerated is ingested - have been tentatively used for the treatment of several autoimmune diseases (where the immune system abnormally attacks parts of the body) with mixed results and the new research, by elucidating the players in gut immuno-tolerance, might help to understand why.

Multicellular animals live peacefully in close contact with a multitude of microorganisms that inhabit their bodies. Humans, for example, have more microorganisms within the body than cells, with just the intestine containing up to 100 trillion microbes, a number about 10 times greater that all our cells. Still, although we remain fully immune competent - so capable of responding to infection by pathogenic microorganisms - we do not react against these “friendly” bacteria. But how do these two opposite immune responses against bacteria so similar exist simultaneously?

In order to understand better this phenomenon Nouara Lhocine, Paulo S. Ribeiro, Francois Leulier and colleagues working in France, London, Switzerland and Portugal used Drosophila (fruit fly) – a common animal model to study human gene functions due to the large numbers of genes shared by the two species - to investigate the possibility that a recently discovered gene – pims – could be involved in this coexistence of tolerance and immuno-reactivity.

In fact, in the Drosophila gut, one of the main responses against bacterial infection is the Imd pathway. The activation of this immune pathway is triggered by peptidoglycans – sugars found on the bacterial wall – and results in the activation of a molecule called Relish. Once activated, Relish induces the expression of several antimicrobial genes to neutralize the invading pathogens. “Friendly” bacteria, on the other hand, despite containing peptidoglycans in their wall exist peacefully inside Drosophila’s gut. The new found gene– pims – was shown to be expressed during bacterial infection in the gut while its inhibition apparently disrupted the Imd pathway suggesting a role in the regulation of this pathway.

Lhocine, Ribeiro, Leulier and colleagues started by analysing pims expression in Drosophila to find it mainly expressed in the gut where it depends on the existence of “friendly” bacteria and activated Relish. These results further suggested – since a basal level of immune response is necessary for pims expression - that this gene acted on the immune response and, specifically, in the gut.

The next step was to analyse what happened to this gut immune response in animals lacking pims. And it was found that, not only these animals showed an immune response against “friendly” bacteria, but also that, during toxic bacterial infection the immune response abnormally spread out of the site of infection risking body injury. These results reveal pims as a negative regulator of the immune response (Imd pathway) granting tolerance to “friendly” gut bacteria, but also assuring that immune responses against infection are contained to the site of infection.

Although the exact mechanism of pims is not fully understood, Lhocine, Ribeiro, Leulier and colleagues were able to show that the peptide produced by pims binds a peptidoglycan receptor, part of the Imd pathway, called PGRP-LCx, . As PGRP-LCx recognition of peptidoglycans activates Imd and ultimately Relish, the outcome of the interaction with Pims is lack of availability to peptidoglycans and consequently suppression of the (Imd) immune response. Results from microscopic observation and separation of the cell’s soluble and insoluble components suggested, however, that PIMS acted, not by destroying PGRP-LCx but by misplacing it, away from its usual localisation – the plasma membrane – resulting in an incapability of the immune system to see peptidoglycans and consequently of getting activated.

Lhocine, Ribeiro, Leulier and colleagues’ results suggest a model where pims is a negative immuno-regulator triggered when specific Imd activation thresholds are reached, after which the immune response is suppressed. It is the existence of this immuno-reactivity threshold that allows the simultaneous existence of tolerance to the gut microorganisms while maintaining immuno-reactivity against infection.. Since peptidoglycans are widely present in bacteria the next question would be to find if the regulatory system here described applies to other host-microorganisms interactions, including those involving humans.

Piece by Catarina Amorim ( catarina.amorim at linacre.ox.ac.uk)

Contacts for the authors of the original paper
Nouara Lhocine
Paulo S. Ribeiro - paulo.ribeiro@icr.ac.uk
Francois Leulier - leulier@cgm.cnrs-gif.fr

Catarina Amorim | alfa
Further information:
http://www.estatisticas.gpeari.mctes.pt
http://www.cellhostandmicrobe.com/content/article/abstract?uid=PIIS1931312808002229

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | 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

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>