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Stealthy leprosy pathogen evades critical vitamin D-dependent immune response
Date:1/29/2012

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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 abi
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Contact: Rachel Champeau
rchampeau@mednet.ucla.edu
310-794-2270
University of California - Los Angeles Health Sciences
Source:Eurekalert  

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