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The mechanism by which the causative agent of leprosy blocks the immune response is deciphered

 
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Last reviewed: 16.10.2021
 
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30 January 2012, 17:27

The causative agent of a terrible disease suppresses the activation of the immune system with vitamin D: instead of running away or disguising themselves from the vigilant eye of immunity, the bacteria seem to order the immune cells to "lay down their arms."

While some bacteria are hiding from immunity with clever camouflage, others avoid a stroke, intercepting the levers of control of the immune system. It is about Mycobacterium leprae, the causative agent of leprosy.

Although leprosy is associated in the philistine mind solely with the "dark Middle Ages", it has successfully survived to the present day: in 2008, for example, 249 thousand new cases were registered. Scientists have studied the symptoms and ways of development of the disease for several centuries, but how the leprosy can prosper, despite the efforts of immunity, has remained a mystery until now.

Researchers from the University of California in Los Angeles managed to decipher the molecular mechanism by which M. Leprae blocks the immune response. It turned out that in this case, the so-called microregulatory mRNAs work. These are very short molecules that, like all RNA, are synthesized on DNA, but do not carry any information about proteins. Instead, they are engaged in regulating the work of other, encoding RNA. MicroRNAs bind to the matrix RNA encoding a particular protein, and suppress protein synthesis on it.

Scientists compared how the two types of infection develop: milder tuberculoid leprosy and more aggressive, all-body lepromatous. It was found that these species differ in the 13 microRNA synthesized by the bacterium. Those RNAs, which were larger in the case of a more severe form, were targeted at genes that control immunity, including the activity of macrophages and T-lymphocytes.

Activation of the immune response depends on vitamin D; its lack in the body contributes to the development of chronic infections and autoimmune diseases. One of the microRNAs, hsa-mir-21, just suppressed the synthesis of the protein responsible for the activation of immunity by vitamin. Once the activity of the microRNA itself was suppressed in macrophages, the ability to eat bacteria immediately returned to these cells. As the researchers write in the journal Nature Medicine, without saving microRNA, the survival of the causal agent of leprosy was reduced fourfold. Thus, leprosy helps in this way in general any infection, not only to itself: scientists have shown that immune cells with the microregulatory RNA of leprosy abandoned in them (it occurs there within 18 hours after the onset of the pathogen) cease to react to the causative agent of tuberculosis. Leprosy, instead of running and hiding from immunity, as if orders him to lay down his arms.

Although this way to "get out of responsibility" by reassigning immune teams seems to be very clever, researchers believe that it is not difficult to neutralize this mechanism: it is enough to combine the neutralization of microRNA with a reinforced dose of vitamin D. However, they do not exclude that many diseases, related to violations of immunity, right up to cancer, are not so much due to a lack of vitamin D, but because of the inability of immune cells to respond to it. Perhaps, in this case, a medicine for leprosy can be useful for fighting a whole spectrum of immunological disorders.

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