Researchers, including one of Indian origin, have identified a new way that the deadly tuberculosis bacteria get into the body, an advance that shows a potential therapeutic angle to explore.
One of the world’s most deadly diseases, tuberculosis – primarily a lung disease – infects more than eight million people and is responsible for 1.5 million deaths each year, researchers said.
According to the Centres for Disease Control and Prevention, approximately one-third of the world’s population is infected with tuberculosis.
The bacterium that causes tuberculosis, Mycobacterium tuberculosis, or Mtb, previously was thought to infect the body only through inhalation and subsequent infection of cells in the lungs, researchers said.
The new study by scientists from UT Southwestern Medical Centre in the US identified an alternative route of entry that could have significant implications for the development of new therapies to prevent tuberculosis infection.
They found that microfold cell (M-cell) translocation is a new and previously unknown mechanism by which Mtb enters the body.
M-cells are specialised epithelial cells that transport particles from the airway or mucosal surface to the compartment below the cell, researchers said.
“The current model of disease is that when Mtb bacteria are inhaled, they reach the end of the lung – the alveolus – and then are ingested by a macrophage, a type of white blood cell that swallows and kills invading bacteria,” said Michael Shiloh from UT Southwestern.
“Our study shows that once Mtb bacteria are inhaled, they also can enter the body directly through M-cells that line the airway tissue, and then travel to the lymph nodes and beyond,” said Shiloh.
“This is a key finding that suggests disease onset outside of alveolar macrophages is not only possible, but also important in the pathogenesis of tuberculosis infection,” he added.
This mechanism of M-cell mediated movement of Mtb may help explain an ancient disease called scrofula. In this disease, tuberculosis infection rarely appears in the lung but instead causes disease in the lymph nodes of the neck.
Preventing Mtb from attaching to receptors on the M-cell surface – such as by vaccinating against a bacterial protein – could block the bacteria’s entry, infection and spread to other organs, said Shiloh.
Researchers currently are working to discover the human cell-surface receptors for Mtb that are involved in the bacteria’s M-cell translocation, as well as to determine the exact machinery used by the cell to move the bacteria from the surface to the bottom of the cell.
“We are taking several experimental approaches to identify the Mtb genes and proteins that are involved in this process,” said Vidhya Nair from UT Southwestern. The findings were published in the journal Cell Reports.