Featured Research

from universities, journals, and other organizations

New enzyme that acts as innate immunity sensor discovered

Date:
February 17, 2013
Source:
UT Southwestern Medical Center
Summary:
Two studies could lead to new treatments for lupus and other autoimmune diseases and strengthen current therapies for viral, bacterial, and parasitic infections.

Two studies by UT Southwestern researchers published in Science magazine could lead to new treatments for lupus and other autoimmune diseases. Shown left to right: Dr. Xiang Chen, research associate in molecular biology and HHMI research specialist I; Dr. Fenghe Du, research associate in molecular biology and a research specialist II at the HHMI; Dr. Lijun “Josh” Sun, assistant professor of molecular biology and HHMI research specialist III; senior author Dr. Zhijian “James” Chen, Dr. Chuo Chen, associate professor of biochemistry; Dr. Heping Shi, postdoctoral researcher of biochemistry; Not pictured: lead author of the cGAMP study Jiaxi Wu, a graduate student of molecular biology.
Credit: Image courtesy of UT Southwestern Medical Center

Two studies by researchers at UT Southwestern Medical Center could lead to new treatments for lupus and other autoimmune diseases and strengthen current therapies for viral, bacterial, and parasitic infections.

The studies identify a new enzyme that acts as a sensor of innate immunity -- the body's first line of defense against invaders -- and describe a novel cell signaling pathway. This pathway detects foreign DNA or even host DNA when it appears in a part of the cell where DNA should not be. In addition, the investigations show that the process enlists a naturally occurring compound in a class known to exist in bacteria but never before seen in humans or other multicellular organisms, said Dr. Zhijian "James" Chen.

Dr. Chen, professor of molecular biology and a Howard Hughes Medical Institute (HHMI) investigator at UTSW, is senior author of both studies available online and published in the February 15 print edition of Science. Although the immune-boosting response of DNA has long been recognized, the mechanism underlying that response remained a mystery, he said.

"In his 1908 Nobel acceptance speech, Ilya Mechnikov noted that surgeons in Europe treated patients with nucleic acids -- the building blocks of DNA -- to boost their patients' immune responses. That observation came four decades before scientists showed that DNA was the carrier of genetic information," Dr. Chen said.

Dr. Chen credits a uniquely biochemical approach for solving the longstanding puzzle. The approach used classical protein purification combined with a modern technology called quantitative mass spectrometry to identify the mysterious compound at the heart of the discovered process.

Under normal conditions, DNA is contained within membrane-bound structures such as the nucleus and mitochondria that are suspended within the cell's soupy interior, called the cytoplasm, he said. DNA in the cytoplasm is a danger signal that triggers immune responses, including production of type-1 interferons (IFN).

"Foreign DNA in the cytoplasm is a sign of attack by a virus, bacteria, or parasite," Dr. Chen said. "Host DNA that somehow leaks into the cytoplasm can trigger autoimmune conditions, like lupus, Sjogren's syndrome, and Aicardi-Goutiere's syndrome in humans."

In these studies, UTSW researchers identified a new sensor of innate immunity -- the enzyme cyclic GMP-AMP synthase (cGAS) -- that sounds a cellular alarm when it encounters DNA in the cytoplasm. After the enzyme detects and binds to the DNA, it catalyzes the formation of a compound called cyclic GMP-AMP (cGAMP), the compound never before seen in humans, Dr. Chen said.

The cGAMP functions as a second messenger that binds to an adaptor protein called STING, which activates a cell signaling cascade that in turn produces agents of inflammation: interferons and cytokines.

"Normally this pathway is important for immune defense against infections by microbial pathogens. However, when the immune system turns against host DNA, it can cause autoimmune diseases," Dr. Chen said. "Our discovery of cGAS as the DNA sensor provides an attractive target for the development of new drugs that might treat autoimmune diseases."

The studies were funded by the National Institutes of Health and by the HHMI.


Story Source:

The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.


Journal References:

  1. L. Sun, J. Wu, F. Du, X. Chen, Z. J. Chen. Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway. Science, 2012; 339 (6121): 786 DOI: 10.1126/science.1232458
  2. J. Wu, L. Sun, X. Chen, F. Du, H. Shi, C. Chen, Z. J. Chen. Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA. Science, 2012; 339 (6121): 826 DOI: 10.1126/science.1229963

Cite This Page:

UT Southwestern Medical Center. "New enzyme that acts as innate immunity sensor discovered." ScienceDaily. ScienceDaily, 17 February 2013. <www.sciencedaily.com/releases/2013/02/130217085033.htm>.
UT Southwestern Medical Center. (2013, February 17). New enzyme that acts as innate immunity sensor discovered. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2013/02/130217085033.htm
UT Southwestern Medical Center. "New enzyme that acts as innate immunity sensor discovered." ScienceDaily. www.sciencedaily.com/releases/2013/02/130217085033.htm (accessed July 29, 2014).

Share This




More Health & Medicine News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
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