Mycobacterium tuberculosis (Mtb), a pathogenic species of bacteria that kills nearly two million people worldwide every year. From the University of Southampton, researchers investigate Mtb’s offensive strategies, which often deal with manipulating the immune system to its advantage.
The bacterium that causes tuberculosis -- Mycobacterium tuberculosis (Mtb) -- may disrupt human immune system regulation processes to promote destruction of lung tissue, according to new research published in PLOS Pathogens. Credit: Brace PT, et al. (2017)
Researchers hypothesized that Mtb was somehow altering immune regulatory pathways designed to prevent an excessive immune response that can lead to autoimmune disease. Past research showed experts that the bacteria could evade the immune system’s efforts to rid the body of disease, but this newest study is focused on how the body influences the immune system to actively make the disease worse.
"Tuberculosis has co-evolved with humans to become an ultimate pathogen, and we identify a mechanism whereby the bacteria disable the 'brakes' of the immune system to cause lung destruction and spread," explained Patience Grace from the University of Southampton.
By extracting human white blood cells and examining the molecular changes when in contact with Mtb, their suspicions were affirmed. They saw Mtb inhibiting a signaling pathway called PI3K/AKT/mTORC1, which is important for regulating the production of a protein called matrix metalloproteinase-1 (MMP-1). This protein contributes to the remodeling of the lung matrix, and its activity is regulated by the PI3K/AKT/mTORC1 pathway. Overactive MMP-1 can lead to lung tissue damage, which is just what Mtb is looking for. The more vulnerable a person’s lung tissue is, the better Mtb can spread and cause disease.
To confirm that Mtb suppresses the PI3K/AKT/mTORC1 pathway, researchers completed study of gene expression in white blood cells extracted from lung tissue in tuberculosis patients. They saw that expression of an important gene from the PI3K/AKT/mTORC1 pathway was lacking. Additionally, they saw that Mtb increases production of MMP-1 in another way: disrupting another signaling pathway, the MAP kinase-interacting kinase (MNK) pathway
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While tuberculosis is thought of as a pulmonary disease, Mtb bacteria are known to infect other parts of the body, including the central nervous system and bone tissue. The immune response to tuberculosis is largely telling of a person’s fate after infection, which is why the present study is so important for scientists interested in developing the most effective treatments for the disease.
The present study was published in the journal PLOS Pathogens.