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 'Icebreaker' protein opens genome for t cell development, Penn researchers find
21.02.2018 | University of Pennsylvania School of Medicine

nachricht Similarities found in cancer initiation in kidney, liver, stomach, pancreas
21.02.2018 | Washington University School of Medicine

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: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Researchers invent tiny, light-powered wires to modulate brain's electrical signals

21.02.2018 | Life Sciences

The “Holy Grail” of peptide chemistry: Making peptide active agents available orally

21.02.2018 | Life Sciences

Atomic structure of ultrasound material not what anyone expected

21.02.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>