ISLAMABAD: Now, a new study uncovers evidence that the disease bacterium disrupts regulatory pathways in white blood cells that limit tissue destruction.

Macrophages are white blood cells that target, engulf, and destroy unwanted agents such as pathogens and unhealthy human cells.

The body needs MMP-1 to help remodel lung tissue (for instance, in wound healing), but if there is too much of the enzyme, it can result in tissue destruction.

The team notes that while the signaling pathways that control MMP-1 in macrophages have already been identified, little is known about what happens to such pathways in tissue infected with TB.

Thus, the researchers set out to find out more by studying the molecular effects of the TB bacterium on isolated macrophages.

They found that the TB bacterium suppresses a signaling pathway called PI3K/AKT/mTORC1 to cause macrophages to release more MMP-1. This pathway helps to regulate MMP-1 so that just enough is released for tissue remodeling without causing tissue destruction.

To confirm that this pathway suppression occurs in humans with TB, the team studied macrophages in lung tissue taken from infected patients.

They found that a gene that needs to be switched on for the pathway to limit MMP-1 production is silent in TB-infected patients, suggesting that this could be what led to lung tissue destruction in these patients.

When they were studying the isolated macrophages, the researchers also found that the TB bacterium disrupts another signaling pathway called MAP kinase-interacting kinase (MNK), the result of which also increases MMP-1 production.

The authors note that their discovery is the first evidence of a link between the MNK pathway and production of the enzyme MMP-1.

An important implication of the study that the authors highlight is the possibility that new and existing TB drugs inadvertently suppress the pathways they identified. Should this be the case, then such drugs may actually promote the spread of TB.

First author Dr. Patience T. Brace, University of Southampton said that "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."