Featured Research

from universities, journals, and other organizations

DNA Arrays Give Clues To Better Vaccines

Date:
February 1, 2002
Source:
Whitehead Institute For Biomedical Research
Summary:
"We are in the midst of a revolution in the way researchers study infectious disease—instead of depending on culture dishes as the only way to observe the behavior of pathogens, scientists are able to eavesdrop on the cross talk between invading microbes and the immune cells of our body," says Richard Young of the Whitehead Institute of Biomedical Research. Young’s lab has done this using DNA microarrays to explore the responses of human macrophages to a variety of bacteria, and as a result, has found clues to making safer, more potent vaccines.

"We are in the midst of a revolution in the way researchers study infectious disease—instead of depending on culture dishes as the only way to observe the behavior of pathogens, scientists are able to eavesdrop on the cross talk between invading microbes and the immune cells of our body," says Richard Young of the Whitehead Institute of Biomedical Research. Young’s lab has done this using DNA microarrays to explore the responses of human macrophages to a variety of bacteria, and as a result, has found clues to making safer, more potent vaccines.

Macrophages, immune cells that are part of the first line of defense, recognize and engulf microbes in a vigilant effort to keep the body healthy. The researchers found that macrophages respond to a broad range of bacteria by sending off an alarm to the rest of the immune system and transforming into a cell primed to mount an immune response.

Further study revealed that the macrophage didn’t have to "see" the whole bacteria to send off its alarm signal, but the presence of specific bacterial components, such as proteins and sugars, induced activation. "These findings will help researchers design therapeutics that will stimulate the immune system in a targeted manner, perhaps with fewer side effects," says Young, lead author on the study, which will appear in the February 5 issue of Proceedings of the National Academy of Sciences.

"The interplay between a person’s immune mechanisms and a microbe’s attempts to circumvent these defenses represents a complex relationship. DNA arrays help researchers dissect this struggle by measuring the activity of many genes in the immune cells as they respond to pathogens. As a result, researchers gain invaluable information about the strengths and vulnerabilities of the microbes and our own immune system during an infection," explains Gerard Nau, a first co-author on the study and a researcher in the Young lab. Ann Schlesinger, postdoctoral fellow in the Young lab, and Joan Richmond, former Young lab member, were also first authors on the paper.

DNA array studies improve our understanding of macrophage defenses, provide insights into disease development, and suggest targets for therapeutic intervention. The researchers found, for instance, that Mycobacterium tuberculosis, the bacteria that cause tuberculosis, fail to activate critical macrophage genes that are involved in fighting bacteria. M. tuberculosis are unique in that they can somehow survive inside the macrophage, only later to escape and cause disease.

It turns out that M. tuberculosis doesn’t trigger the macrophage response to produce IL-12 and IL-15, like other bacteria do. IL-12 plays a fundamental role in activating another arm of the immune system called T helper responses and is critical for host resistance to tuberculosis infection in mice and humans. The lack of strong IL-12 response in macrophages indicates that this may be one way M. tuberculosis evades host defenses and supports the use of both IL-12 and IL-15 in clinical tuberculosis therapies, as suggested by animal models.

The researchers also found interesting specifics about the shared macrophage activation program, which was induced by a wide range of bacteria, including Gram-positive, Gram-negative, and mycobacteria. While the activation program seemed to trigger a generic alarm, which called on other antibacterial defenses of the immune system, the majority of changes triggered in the macrophage involved cell surface proteins and signaling molecules. Such changes generate new functions in the macrophage, suggesting a maturation process similar to that observed with other immune cells.

Interestingly, the presence of certain bacterial components was enough to activate the alarm signal. This suggests promising new adjuvants (compounds that make a vaccine more potent by increasing an immune response) that could be used in vaccine development. The list includes heat shock proteins, which supports their use in preclinical and clinical vaccine trials.

The bacterial components that set off the alarm signal activated a family of proteins called Toll-like receptors (TLRs), suggesting that small molecule drugs designed to activate this receptor may provide a new therapeutic approach.

"DNA microarray data is providing us with unprecedented details about our own immune defense cells as they orchestrate a response to attacking bacterial pathogens that are responsible for some of the major diseases of mankind," says Young. "This information should lead to new therapeutic strategies against these diseases."


Story Source:

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


Cite This Page:

Whitehead Institute For Biomedical Research. "DNA Arrays Give Clues To Better Vaccines." ScienceDaily. ScienceDaily, 1 February 2002. <www.sciencedaily.com/releases/2002/01/020130073914.htm>.
Whitehead Institute For Biomedical Research. (2002, February 1). DNA Arrays Give Clues To Better Vaccines. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/2002/01/020130073914.htm
Whitehead Institute For Biomedical Research. "DNA Arrays Give Clues To Better Vaccines." ScienceDaily. www.sciencedaily.com/releases/2002/01/020130073914.htm (accessed October 23, 2014).

Share This



More Health & Medicine News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
US to Track Everyone Coming from Ebola Nations

US to Track Everyone Coming from Ebola Nations

AP (Oct. 22, 2014) Stepping up their vigilance against Ebola, federal authorities said Wednesday that everyone traveling into the US from Ebola-stricken nations will be monitored for symptoms for 21 days. (Oct. 22) Video provided by AP
Powered by NewsLook.com
Doctors Help Paralysed Man Walk Again, Patient in Disbelief

Doctors Help Paralysed Man Walk Again, Patient in Disbelief

AFP (Oct. 22, 2014) Polish doctors describe how they helped a paralysed man walk again, with the patient in disbelief at the return of sensation to his legs. Duration: 1:04 Video provided by AFP
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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