A key element in understanding how human lungs fight TB has been unlocked, which could be crucial with the onset of an antibiotic resistance.
In an effort to help prevent an outbreak of drug-resistant tuberculosis (TB), a team of Irish and UK researchers has identified the way that TB hijacks our immune cells in the early stages of infection.
Involving researchers from Trinity College Dublin (TCD), the aim of the project was to unlock the secrets of how exactly the lungs fight off TB naturally as, very soon – and without the development of new medication – it could be the only available option.
In Ireland alone, there have been dozens of cases of multi-drug-resistant TB and four cases of extreme drug-resistant TB in recent months, as antibiotic resistance rises globally with no effective new drugs set to go to market.
While it is the world’s number one infectious killer, half of the infected people clear the invading mycobacteria (TB bacteria) after inhaling it into their lungs and, until now, how this works has remained a mystery.
Similarities found in zebrafish cells
In a paper published to the journal Immunity, the researchers used transparent zebrafish to track mycobacteria in real time and identified which cells they infected at different stages of the disease.
It then became apparent that the more virulent strains of mycobacteria were able to hijack the macrophage immune cells in the lung, causing them to produce a protein that attracts white blood cells from the circulation. These white blood cells fuse with the macrophages and, in turn, become infected.
The TCD team used donated lung samples to study the response of the human immune system to TB in the early stages of infection. Tests showed that human alveolar macrophages behave similarly to zebrafish macrophages, producing the same protein that attracts white blood cells to the lung.
However, unlike the resident alveolar macrophages, these white blood cells lack the ability to curb the mycobacteria growth that leads to inflammation and the spread of the infection.
Dr Seónadh O’Leary, one of those involved in the TCD team, said: “We are fascinated how TB bacteria virulence factors can corrupt this human lung immune cell, which is ordinarily exceptionally good at clearing infection.
“This allows us to continue in our research to design novel ways to support the effective lung cell and prevent infections in exposed people.”