A new study led by researchers from New York University found that bacteria that causes tuberculosis actually tricks healthy immune cells into masking their presents in the body and sustaining them. The fact that these cells not only hide but create food for themselves is what makes TB so difficult to fight.
Mycobacterium tuberculosis continues to be the leading bacterial cause of death on a global scale. Just like HIV, TB successfully tricks immune cells that are meant to destroy the bacteria into being unable to detect the virus.
The study published in Nature Immunology targeted the ongoing battle between the human immune system and successful pathogens that go beyond simply evasion but take over immune cell functioning. Researchers describe how tuberculosis bacteria cause mammalian immune cells (also known as macrophages) to create more genetic material known as microRNA-33 (or miRNA-33). These materials make macrophages unable to “mark” TB bacteria as an enemy, meaning they will no longer destruct on sight. These genetic changes also cause cells to build more fat, which the TB proceeds to use to feed on. Studies were done on mice but the same mechanisms were found within human macrophages of those infected with tuberculosis.
Senior Study author Kathryn Moore, PhD, the Jean and David Blechman Professor of Cardiology at NYU Langone says the results of the study describe mechanisms that are so precise they enable TB to remain in the body. She says this is what makes the infection so deadly and while anti-cholesterol medications are being investigated as future treatment solutions, the study points to other ways by which reversal of TB forcing cells to build fat may be available to target the disease. This would take away a majority of the power the disease has over the body.
The new study found that TB bacteria proteins trigger an immune signaling pathway within macrophages. Inside, a protein complex named NFKappaB triggers key genes to create more microRNA-33. This drastically weakens the signal sent by many autophagy genes that would typically maintain fat levels.
Thanks to the new knowledge that TB may require additional fat within the body in order to not only survive, but thrive, there is hope that statins may be used against TB. These cholesterol inhibitors may be able to fight back with lipid build up within macrophages. In 2010, Moore’s team published a paper in Science magazine that says miR-33 are encoded in the same gene that statins appear.
Researchers believe it is possible that bacterial lipid effect may be prevented using antisense oligonucleotides. These are molecular chains that are the proper shape to not only latch onto but remove miR-33. Mipomersen, for example, is already used to treat health concerns that lead to high cholesterol.
The problem with the treatment of TB is it is going to be difficult to develop an inexpensive solution that will be something developing countries can afford, says Moore. More attention must be gathered and not just that, but getting the industry to engage in working on a disease that is rare in the United States is a difficult task to take on. At this point in time, antisense oligonucleotide injectable drugs are very pricey.
The team is currently focusing their energy on locating drugs that can be tested on mice infected with TB. The hope is to find drugs that can not only lower levels of miR-33 but also boost pathways that are currently suppressed by TB due to RNA.