Featured Research

from universities, journals, and other organizations

Endogenous antibiotic discovered in the brain

Date:
May 6, 2013
Source:
Université du Luxembourg
Summary:
Scientists have discovered that immune cells in the brain can produce a substance that prevents bacterial growth: namely itaconic acid. Until now, biologists had assumed that only certain fungi produced itaconic acid.Scientists have now shown that even so-called microglial cells in mammals are also capable of producing this acid.

Scientists from the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg have discovered that immune cells in the brain can produce a substance that prevents bacterial growth: namely itaconic acid. Until now, biologists had assumed that only certain fungi produced itaconic acid. A team working with Dr. Karsten Hiller, head of the Metabolomics Group at LCSB, and Dr. Alessandro Michelucci has now shown that even so-called microglial cells in mammals are also capable of producing this acid. "This is a ground breaking result," says Prof. Dr. Rudi Balling, director of LCSB: "It is the first proof of an endogenous antibiotic in the brain."

The researchers have now published their results in the scientific journal PNAS.

Alessandro Michelucci is a cellular biologist, with focus on neurosciences. This is an ideal combination for LCSB with its focus on neurodegenerative diseases, and Parkinson's disease especially -- i.e. changes in the cells of the human nervous system. "Little is still known about the immune responses of the brain," says Michelucci. "However, because we suspect there are connections between the immune system and Parkinson's disease, we want to find out what happens in the brain when we trigger an immune response there." For this purpose, Michelucci brought cell cultures of microglial cells, the immune cells in the brain, into contact with specific constituents of bacterial membranes. The microglial cells exhibited a response and produced a cocktail of metabolic products.

This cocktail was subsequently analysed by Karsten Hiller´s metabolomics group. Upon closer examination, the scientists discovered that production of one substance in particular -- itaconic acid -- was upregulated. "Itaconic acid plays a central role in the plastics production. Industrial bioreactors use fungi to mass-produce it," says Hiller: "The realisation that mammalian cells synthesise itaconic acid came as a major surprise."

However, it was not known how mammalian cells can synthesise this compound. Through sequence comparisons of the fungi's enzyme sequence to human protein sequences, Karsten Hiller then identified a human gene, which encodes a protein similar to the one in fungi: immunoresponsive gene 1, or IRG1 for short -- a most exciting discovery as the function of this gene was not known. Says Hiller: "When it comes to IRG1, there is a lot of uncharted territory. What we did know is that it seems to play some role in the big picture of the immune response, but what exactly that role was, we were not sure."

To change this situation, the team turned off IRG1 in cell cultures and instead added the gene to cells that normally do not express it. The experiments confirmed that in mammals, IRG1 codes for an itaconic acid-producing enzyme. But why? When immune cells like macrophages and microglial cells take up bacteria in order to inactivate them, the intruders are actually able to survive by using a special metabolic pathway called the glyoxylate shunt. According to Hiller, "macrophages produce itaconic acid in an effort to foil this bacterial survival strategy.

The acid blocks the first enzyme in the glyoxylate pathway. Which is how macrophages partially inhibit growth in order to support the innate immune response and digest the bacteria they have taken up." LCSB director Prof. Dr. Rudi Balling describes the possibilities that these insights offer: "Parkinson's disease is highly complex and has many causes. We now intend to study the importance of infections of the nervous system in this respect -- and whether itaconic acid can play a role in diagnosing and treating Parkinson's disease."


Story Source:

The above story is based on materials provided by Université du Luxembourg. Note: Materials may be edited for content and length.


Journal Reference:

  1. A. Michelucci, T. Cordes, J. Ghelfi, A. Pailot, N. Reiling, O. Goldmann, T. Binz, A. Wegner, A. Tallam, A. Rausell, M. Buttini, C. L. Linster, E. Medina, R. Balling, K. Hiller. Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1218599110

Cite This Page:

Université du Luxembourg. "Endogenous antibiotic discovered in the brain." ScienceDaily. ScienceDaily, 6 May 2013. <www.sciencedaily.com/releases/2013/05/130506095253.htm>.
Université du Luxembourg. (2013, May 6). Endogenous antibiotic discovered in the brain. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2013/05/130506095253.htm
Université du Luxembourg. "Endogenous antibiotic discovered in the brain." ScienceDaily. www.sciencedaily.com/releases/2013/05/130506095253.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) — Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) — Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) — At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Xtreme Eating: Your Daily Caloric Intake All On One Plate

Xtreme Eating: Your Daily Caloric Intake All On One Plate

Newsy (July 30, 2014) — The Center for Science in the Public Interest released its 2014 list of single meals with whopping calorie counts. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



    Save/Print:
    Share:  

    Free Subscriptions


    Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

    Get Social & Mobile


    Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

    Have Feedback?


    Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
    Mobile iPhone Android Web
    Follow Facebook Twitter Google+
    Subscribe RSS Feeds Email Newsletters
    Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins