A molecular switch for stomach disease

January 08, 2020

Infectious diseases triggered by bacteria and other microbes are the most frequent cause of human mortality across the globe. Roughly half of the world's population carry the bacteria Helicobacter pylori (H. Pylori) in their stomach, known to be the most significant risk factor for ulcers, MALT lymphoma and adenocarcinoma in the stomach. The rapid spread of pathogens resistant to medication such as antibiotics is making it increasingly difficult to treat infections such as these using antimicrobial therapies. A research team from Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) has now revealed a new mechanism which controls the causes of infection with H. Pylori, triggering the development of stomach diseases. It is hoped that these findings will lead in time to new therapies. The study was published in the journal Nature Communications.

A team of national and international scientists led by Prof. Dr. Steffen Backert from the Chair of Microbiology at FAU has investigated how the bacteria manipulate the host's immune system in order to ensure their long-term survival in the stomach. A chronic inflammation is the most common cause for stomach illnesses such as these. The researchers have identified a 'molecular switch' which uses a previously unknown mechanism to regulate the inflammation reaction in the stomach. The interaction between H. Pylori and stomach cells activates a syringe-like pilus structure referred to as a type IV secretion system. A protein, CagL, is presented at the surface of this structure which allows the bacterial toxin known as CagA protein to be delivered into the stomach cells. The injected CagA then re-programmes the host cell so that stomach cancer can develop. It now appears that CagL also has another important function, however. The protein is recognised by the immune system via the receptor TLR5. Experiments in mouse models have demonstrated that TLR5 controls the infection efficiently. CagL imitates a TLR5 recognition motif in the flagellin protein of other pathogens, thereby controlling the human immune response.

Interestingly, this signalling pathway can be both switched on and switched off by the type IV secretion system, which is not thought to be the case with other bacteria. Presumably, H. Pylori has exploited this signalling pathway over thousands of years of evolution to eliminate 'bothersome' bacterial competitors in the stomach. At the same time, CagL influences the congenital and adaptive immune system as well as the inflammation reaction in such a way that H. Pylori itself is not recognised and therefore cannot be eliminated - a mechanism which is crucial for long-term infections with H. Pylori in the stomach and triggering stomach disease. Researchers also observed that TLR5 is no longer produced in healthy stomach cells and once an infection has been resolved. This indicates that the expression of this protein is a new indicator for stomach disease in humans triggered by H. Pylori.

New approach for treating stomach disease

Prof. Backert hopes that these findings will help develop significant new approaches for anti-bacterial treatment, as CagL, CagA and TLR5 lend themselves well to treatment. The participating researchers have already started to test appropriate substances. 'We hope that specific inhibitors can paralyse the function of the type IV secretion system, or partially or entirely prevent infection,' reports Prof. Backert.
-end-
The publication is the result of many years of research at the Chair of Microbiology at FAU funded by the German Research Foundation as part of Collaborative Research Centre (SFB) 1181 'Schaltstellen zur Auflösung von Entzündung' (switching points for resolving inflammation) and carried out in collaboration with other working groups from Germany, Switzerland, Korea and India.

University of Erlangen-Nuremberg

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.