Featured Research

from universities, journals, and other organizations

Molecular Component Of Innate Immunity Discovered

Date:
April 9, 2005
Source:
The Scripps Research Institute
Summary:
In a paper appearing in this week’s issue of the journal Nature, Professor Bruce Beutler, M.D., Research Associate Kasper Hoebe, Ph.D., and their colleagues at The Scripps Research Institute in La Jolla, CA have identified one of the molecules that mediates innate immune recognition.

La Jolla, CA, February 3, 2005 -- “There is no need to be a doctor or a scientist to wonder why the human body is capable of resisting so many harmful agents in the course of everyday life,” the great Russian immunologist Ilya Mechnikov stated in his 1908 Nobel prize acceptance speech. And indeed he was right—how in the world do we survive?

Humans, like all higher organisms, are constantly challenged in a world filled with microbial pathogens. We are bathed in bacteria, confronted with fungi, pilloried with parasites, and invaded by viruses. And yet, most of the time, we survive.

One reason we do, as Mechnikov was one of the first to discover, is that we possess an ancient and crucial physiology known as innate immunity that is active in eukaryotic organisms as diverse as humans and fruit flies. In fact, Mechnikov discovered innate immunity in starfish, when he observed “phagocytic” starfish cells such as macrophages, which could engulf and destroy foreign pathogens.

In the century that followed Mechnikov’s work, much of the broad picture of innate immunity has become clear. Broadly speaking, the recognition of foreign antigen triggers the immune system, which responds with a multi-stage biochemical defense starting with the unleashing of an army of white blood cells, like macrophages, which engulf and destroy pathogens. The macrophages also fight the pathogens by producing large amounts of chemicals that induce inflammation and help the body clear the infection.

But many of the details of the molecules and signaling pathways that allow this vigorous immune defense are still being elucidated.

Now, in a paper appearing in this week’s issue of the journal Nature, Professor Bruce Beutler, M.D., Research Associate Kasper Hoebe, Ph.D., and their colleagues at The Scripps Research Institute in La Jolla, CA have identified one of the molecules that mediates innate immune recognition—CD36.

Uncovering CD36’s Role

Normally, when human or mouse cells encounter bacteria or viruses, they recognize proteins, lipids, or other molecular components of these foreign invaders through a family of receptor proteins called the toll-like receptors (TLRs). Humans have at least 10 different TLRs, and one of Beutler’s goals is to identify how these receptors and associated immune molecules such as CD36 mediate innate immunity.

One way he has approached this is through a technique known as positional cloning, which combines classical genetic mapping methods with high-powered computer-aided searches to identify relevant genes.

"We're attempting to create mutations that destroy innate immunity and in this way, to identify all of the genes involved in innate immunity or at least as many as we can,” Beutler says. “[When] we find a model that is immunocompromised we can go back and positionally clone the critical gene that we have hit."

About two years ago, they detected a genetic mutation termed oblivious that renders its carriers’ macrophages unable to detect a molecule called MALP-2, which is produced by the bacterium Mycoplasmapneumoniae, and unable to detect a crude preparation of commercial peptidoglycan derived from the bacterium Staphylococcus aureus.

This mutation weakened the innate immune systems of the mice, which are immunodeficient and highly susceptible to bacterial infections. Using positional cloning, Beutler, Hoebe, and their colleagues mapped the oblivious mutation to an obscure gene CD36, which has an equivalent gene in humans

CD36 is produced by various types of cells associated with the blood and the immune system. It can be found expressed in mammals both on the surface of blood platelets and on endothelial cells lining the blood vessels, where it is used for platelet adhesion. Previously, CD36 had been identified on the surface of innate immune cells as a class II scavenger—it scavenges or removes potentially dangerous endogenous molecules from the body, such as human proteins that have become oxidized or cross-linked.

Given CD36’s role in recognizing both endogenous human molecules and exogenous bacterial molecules, Beutler, Hoebe, and their colleagues suggest that it may be a mediator of what is known as a sterile inflammation, in which immune cells release inflammatory chemicals in the absence of any infection. Sterile inflammation is a condition common to many different diseases, including autoimmune diseases.

It is still not clear whether TLRs are involved in sterile inflammation, but CD36’s involvement strongly suggests that they may be. If that is the case, then scientists will have a potentially valuable target for the design of drugs aimed at treating diseases involving sterile inflammation. By designing a way to block some part of the TLR signaling pathway, they might succeed at reducing sterile inflammation and ameliorating some of the diseases it causes.

The article, “CD36 is a sensor of diacylglycerides” is authored by Kasper Hoebe, Philippe Georgel, Sophie Rutschmann, Xin Du, Suzanne Mudd, Karine Crozat, Sosathya Sovath, Louis Shamel, Thomas Hartung, Ulrich Zδhringer, and Bruce Beutler and appears in the February 3, 2005 issue of the journal Nature. See: http://www.nature.com.

This work was supported by the National Institutes of Health.


Story Source:

The above story is based on materials provided by The Scripps Research Institute. Note: Materials may be edited for content and length.


Cite This Page:

The Scripps Research Institute. "Molecular Component Of Innate Immunity Discovered." ScienceDaily. ScienceDaily, 9 April 2005. <www.sciencedaily.com/releases/2005/03/050326002258.htm>.
The Scripps Research Institute. (2005, April 9). Molecular Component Of Innate Immunity Discovered. ScienceDaily. Retrieved August 23, 2014 from www.sciencedaily.com/releases/2005/03/050326002258.htm
The Scripps Research Institute. "Molecular Component Of Innate Immunity Discovered." ScienceDaily. www.sciencedaily.com/releases/2005/03/050326002258.htm (accessed August 23, 2014).

Share This




More Health & Medicine News

Saturday, August 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) — An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Two US Ebola Patients Leave Hospital Free of the Disease

Two US Ebola Patients Leave Hospital Free of the Disease

AFP (Aug. 21, 2014) — Two American missionaries who were sickened with Ebola while working in Liberia and were treated with an experimental drug are doing better and have left the hospital, doctors say on August 21, 2014. Duration: 01:05 Video provided by AFP
Powered by NewsLook.com
Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) — Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
American Ebola Patients Released: What Cured Them?

American Ebola Patients Released: What Cured Them?

Newsy (Aug. 21, 2014) — It's unclear whether the American Ebola patients' recoveries can be attributed to an experimental drug or early detection and good medical care. 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