Stealthy leprosy pathogen evades critical vitamin D-dependent immune response
Skin biopsy sections from L-lep (progressive disease) and T-lep (limited disease) show the micro RNA hsa-mir-21 identified through a green fluorescent stain and skin nuclei identified with a blue fluorescent stain. Note more occurrence of hsa-mir-21 in progressive versus limited disease. Credit: UCLA
A team of UCLA scientists has found that the pathogen that causes leprosy has a remarkable ability to avoid the human immune system by inhibiting the antimicrobial responses important to our defenses.
In one of the first laboratory studies of its kind, researchers discovered that the leprosy pathogen Mycobacterium leprae was able to reduce and evade immune activity that is dependent on vitamin D, a natural hormone that plays an essential role in the body's fight against infections.
The pathogen manipulated micro-RNAs, tiny molecules made of ribonucleic acids that carry information and that help regulate genes to direct cell activity, including immune system defenses. Micro-RNAs are short RNAs that do not code information for proteins, which carry out all cell activity; rather, they bind to the RNAs that do code for proteins and block them.
Published in the Jan. 29 online edition of the journal Nature Medicine, the findings demonstrate how an infectious disease pathogen like M. leprae can use micro-RNAs to impact the immune system's fight response.
"We may find that these tiny micro-RNAs can be exploited by pathogens to weaken our immune response," said the study's first author, Dr. Philip T. Liu, an assistant professor of medicine at the Orthopaedic Hospital Research Center and in the department of dermatology at the David Geffen School of Medicine at UCLA. "By better understanding how pathogens can escape our immune cells, we can design more effective therapies to boost our immune responses to these difficult to treat infections like leprosy."
Leprosy, one of the world's oldest known diseases, is a chronic infectious disease that affects the skin, the peripheral nerves, the upper respiratory tract and the eyes and can lead to disfigurement of the hands, face and feet. In 2008, approximately 249,000 new cases of leprosy were reported worldwide, according to the World Health Organization.
For the study, researchers compared the micro-RNAs in human skin lesions from two types of leprosy: tuberloid leprosy, a milder infection that is more easily contained, and lepromatous leprosy, which is more serious and causes widespread infection throughout the body.
In the lab, the scientists identified 13 micro-RNAs that differed between the two types of leprosy. The micro-RNAs that were found to be more common in lepromatous leprosy seemed to target the genes important for directing key immune system cells, including macrophages and T cells.
The team found that a particular micro-RNA, hsa-mir-21, inhibited the gene activity of the vitamin Ddependent immune pathway used to help fight infection. When researchers neutralized the activity of hsa-mir-21 in macrophages, the cells were able to kill the bacteria again.
"The leprosy pathogen was able to effectively evade the host's immune response by regulating critical immune system genes," said senior investigator Dr. Robert Modlin, UCLA's Klein Professor of Dermatology and chief of dermatology at the Geffen School of Medicine. "It's like having the enemy sending a decoy message to your combat troops and telling them to lower their weapons."
To test the significance of this micro-RNA with other infectious diseases, the researchers also introduced hsa-mir-21 to human macrophages that were then infected with tuberculosis in the lab. Researchers found that the micro-RNA similarly blocked the ability of the macrophages to kill the bacteria.
Researchers also demonstrated that immune activation of the leprosy-infected immune cells decreased the leprosy bacteria's viability four-fold but only when hsa-mir-21 activity was silenced. In fact, an over-expression of this micro-RNA blocked immune activity, resulting in a five-fold increase in bacterial viability.
"We were surprised at the devastating effects that even a single micro-RNA had on the ability of immune cells to fight the infections," Liu said.
In addition, the team showed that this micro-RNA was found in human immune cells only 18 hours after the onset of leprosy infection. The presence of the micro-RNA so early in the infection suggests it might play a role in actual disease development, the researchers said.
Further investigation of this single micro-RNA in leprosy may provide a framework for analyzing other micro-RNAs to help determine their cumulative role in regulating the immune response.
The micro-RNAs are small, and therefore it is possible to develop treatments which neutralize them, the researchers said.
"We may find that a combination of vitamin D supplementation with a genetically targeted therapy could provide an optimal treatment approach to leprosy and possibly other chronic infectious diseases," said Modlin, who also serves as vice chair for cutaneous medicine and dermatological research at UCLA and is a distinguished professor of medicine and of microbiology, immunology and molecular genetics.
"Vitamin D insufficiency has been associated with a number of infectious and autoimmune diseases, cardiovascular disease and cancers," Modlin added. "Our study indicates that micro-RNAs can alter human vitamin D responses and contribute to disease pathology."
Dr. Barry Bloom of Harvard University, who was not an author of this study but is part of the research team studying this field, agreed.
"Such a novel approach may be especially worth exploring in treatment of drug-resistant pathogens such as some forms of tuberculosis, where antimicrobial therapy is becoming increasingly problematic," Bloom said.
Provided by University of California - Los Angeles
- AIDS drugs reveal leprosy infections Oct 24, 2006 | not rated yet | 0
- Leprosy susceptibility genes reported Dec 16, 2009 | not rated yet | 0
- Genetic variant offers protection against TB and leprosy Mar 04, 2010 | not rated yet | 0
- Scientists find vitamin D crucial in human immune response to tuberculosis Oct 12, 2011 | not rated yet | 0
- Micro-RNAs Are Life’s Genetic Sculptors Feb 26, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Image of a Convex Lens Cut in Half Horizontally
3 hours ago Hello everyone, A friend of mine came up with this question in class and I really do not have a good answer. Suppose you have a convex lens...
Ray tracing throught optical system of thick lenses
3 hours ago Can you advise me a free software that allow to draw rays passed throught system of thick lenses (preferable in 3D)?
Faraday's law on circular wire
4 hours ago In my examples on Faraday's law in my book, they use a drawing of a magnet approaching a circular wire. The changing magnetic flux then induces an...
Specific Exergy vs Specific Flow Exergy
5 hours ago I'm having some difficulty understanding exactly what the difference between the definitions of these values are. As I understand it, in terms of...
The Durability of Bone: Long Falls
14 hours ago I am doing a paper on the physics in Valve's Portal and got interested in the "Long Fall Boots" that prevent any damage no matter how far you fall. I...
Is energy convertible to matter?
15 hours ago Can we convert energy to matter?
- More from Physics Forums - Classical Physics
More news stories
(Medical Xpress)—A research team, led by Jeremy Barr, a biology post-doctoral fellow, unveils a new immune system that protects humans and animals from infection.
Immunology May 20, 2013 | 4.8 / 5 (22) | 8 |
(Medical Xpress)—Scientists at King's College London have discovered that Vitamin D has the potential to significantly reduce the symptoms of asthma. The study, led by Professor Catherine Hawrylowicz from ...
Immunology May 20, 2013 | 5 / 5 (1) | 0 |
Melbourne researchers have identified an immune protein that has the potential to stop or reverse the development of type 1 diabetes in its early stages, before insulin-producing cells have been destroyed.
Immunology May 20, 2013 | 5 / 5 (5) | 0 |
Raising hopes for cell-based therapies, UC San Francisco researchers have created the first functioning human thymus tissue from embryonic stem cells in the laboratory. The researchers showed that, in mice, ...
Immunology May 16, 2013 | 4.8 / 5 (5) | 0 |
Researchers from CNRS, Université Toulouse III - Paul Sabatier and IRD have elucidated new molecular mechanisms involved in resistance to visceral leishmaniasis, a serious parasitic infection. They have shown that dectin-1 ...
Immunology May 16, 2013 | not rated yet | 0
Researchers at Johns Hopkins have unraveled the molecular foundations of cocaine's effects on the brain, and identified a compound that blocks cravings for the drug in cocaine-addicted mice. The compound, already proven safe ...
5 minutes ago | not rated yet | 0 |
Scientists have reversed behavioral and brain abnormalities in adult mice that resemble some features of schizophrenia by restoring normal expression to a suspect gene that is over-expressed in humans with ...
5 minutes ago | not rated yet | 0 |
Costs to treat stroke are projected to more than double and the number of people having strokes may increase 20 percent by 2030, according to the American Heart Association/American Stroke Association.
5 minutes ago | not rated yet | 0
University of Granada scientists have patented a new treatment for acne that is based on completely natural substances and is much more effective than artificial formulas because it does not create resistance ...
12 minutes ago | not rated yet | 0
The new 13-valent pneumococcal conjugate vaccine (PCV13) appears to be as safe as the previous version used prior to 2010, the 7-valent pneumococcal conjugate vaccine (PCV7), according to a Kaiser Permanente study published ...
1 hour ago | not rated yet | 0
Is it permissible to harm one to save many? Those who tend to say "yes" when faced with this classic dilemma are likely to be deficient in a specific kind of empathy, according to a report published in the scientific journal ...
7 hours ago | not rated yet | 0 |