Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Newly Identified Mechanism Helps Explain Why People of African Descent Are More Vulnerable to TB

24.02.2006


A team of scientists has identified a cellular mechanism that may help explain the puzzle of why people of African descent are more susceptible to tuberculosis infection and why, once infected, they develop more severe states of the disease than whites. The team includes researchers from University of California, Los Angeles (UCLA), and Harvard School of Public Health (HSPH). The paper will appear online in the February 23 issue of Science Express.



Approximately eight million people worldwide are infected with TB annually, with an estimated two million people dying from the lung disease each year. TB is caused by the pathogen Mycobacterium tuberculosis, but infection does not automatically result in full-blown disease. In the U.S., minority and foreign-born populations have significantly higher rates of TB than the overall U.S. average, according to the Centers for Disease Control and Prevention. In 2004, African Americans had TB case rates that were eight times higher than whites.

Scientists have understood that mice -- a frequently used animal model in experiments -- combat microbes such as TB by producing nitric oxide in scavenger cells of the immune system known as macrophages. However, this mechanism is not prominent in humans, and the mechanism by which human macrophages kill the tubercle bacillus has remained an additional puzzle. Innate immunity is the rapid immune response of host scavenger cells to recognition of certain patterns of molecules found on pathogens, which has been retained in evolution from fruit flies to humans. A set of receptors on macrophages in humans called Toll-like receptors contribute to innate immune responses. The researchers describe a novel pathway used by human macrophages that may be critical to resisting infection with certain pathogens and that turns out to be critically dependent on vitamin D. This description provides a different way to think about how human immune systems battle pathogens in general.


The research team found that when Toll-like receptors in humans are stimulated by specific molecules of the tubercle bacillus, vitamin D receptors and an enzyme called Cyp27B1, which converts the vitamin from an inactive form to an active form, are dramatically increased. The result of this dual activation is the cleavage of a preexistent protein to a small peptide called cathelicidin, which can kill TB bacilli in the test tube. One of the interesting aspects of this mechanism is that production of vitamin D in humans is dependent on exposure to UV light, generally sunlight, and may not have evolved in mice since they are nocturnal animals.

"These studies began with a very basic exploration of differences in gene expression in two related human white blood cell types known to be involved in host responses to infection, and concluded by revealing a new and potentially important human mechanism for killing intracellular pathogens,” said Philip Liu, postdoctoral scholar in the Department of Immunology and Molecular Genetics at the David Geffen School of Medicine at UCLA and co-lead author of the paper.

African Americans have significantly lower levels of vitamin D in their blood serum than whites because higher levels of melanin -- the pigment that provides color to skin absorbs UV light and reduces African Americans’ ability to produce vitamin D. When the macrophages were stimulated by molecules of the tubercle bacillus that trigger Toll-like receptors, the research team found that cells cultured in serum provided by African Americans produced 63 percent less of the microbe-killing cathelicin than when cultured in serum from whites. Supplementing the serum from African Americans with vitamin D precursor to a range found in serum samples from whites boosted the induction of cathelicidin.

Scientists have long known that African Americans have less vitamin D than whites and that they are more vulnerable to TB. This study helps to resolve two of the puzzles of tuberculosis, the differences between mice and human antibacterial mechanisms, and the susceptibility of people of African and possibly Asian descent to tuberculosis. The researchers suggest a need for clinical trials to investigate the effect of vitamin D supplementation.

“Our results indicate that we have much yet to learn about human immune responses to infections. They also emphasize the importance of vitamin D in human immune responses, and suggest that it is now important to learn how much vitamin D is optimal for innate immunity, and how that can best be achieved through diet or supplementation,” said the senior investigator of these studies, Dr. Robert Modlin, Klein Professor of Dermatology and Professor of Microbiology, Immunology and Molecular Genetics at the David Geffen School of Medicine at UCLA.

“Tuberculosis is a devastating disease that strikes vulnerable populations particularly hard," said immunologist Barry R. Bloom, Dean of the Faculty at HSPH and a co-author of the paper. "This study provides a new mechanism for innate immunity in humans and demonstrates how variations in vitamin D synthesis may make individuals susceptible to TB infection. It is exciting to consider the possibility that innate immunity to tuberculosis and other infections in vulnerable populations might be enhanced by providing a simple vitamin that would cost only pennies a day.”

This research was supported by grants from the National Institutes of Health and the German Research Foundation.

For further information contact:
Harvard School of Public Health
677 Huntington Avenue
Boston, MA 02115
Contact: Robin Herman
rherman@hsph.harvard.edu
(617) 432-4752

UCLA Health Sciences Media Relations
924 Westwood Blvd., Ste. 350
Los Angeles, CA 90095-7301
Contact: Rachel Champeau
rchampeau@mednet.ucla.edu
(310) 794-2270 or (310) 794-0777

Harvard School of Public Health is dedicated to advancing the public’s health through learning, discovery, and communication. More than 300 faculty members are engaged in teaching and training the 900-plus student body in a broad spectrum of disciplines crucial to the health and well being of individuals and populations around the world. Programs and projects range from the molecular biology of AIDS vaccines to the epidemiology of cancer; from risk analysis to violence prevention; from maternal and children’s health to quality of care measurement; from health care management to international health and human rights.

Robin Herman | EurekAlert!
Further information:
http://www.hsph.harvard.edu

More articles from Health and Medicine:

nachricht Penn study identifies new malaria parasites in wild bonobos
21.11.2017 | University of Pennsylvania School of Medicine

nachricht NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Previous evidence of water on mars now identified as grainflows

21.11.2017 | Physics and Astronomy

NASA's James Webb Space Telescope completes final cryogenic testing

21.11.2017 | Physics and Astronomy

New catalyst controls activation of a carbon-hydrogen bond

21.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>