How does Mycobacterium tuberculosis infect the lung?

Tuberculosis (TB) is the most common major infectious disease today. It is estimated that two billion people--or one-third of the world's population--are chronically infected without active symptoms. Nine million new cases of active disease are diagnosed annually, resulting in two million deaths. TB is predominantly a lung disease. It is caused by a microbe called Mycobacterium tuberculosis which infects lung cells, but it is still not clear how exactly this happens. Ludovic Tailleux, Olivier Neyrolles, and colleagues (from the Pasteur Institute, in collaboration with the Necker and Saint-Louis Hospitals, in Paris) have found that a molecule called DC-SIGN plays a crucial part.

The researchers wanted to examine whether lung cells from patients with TB were different from those of healthy people or those with different lung diseases, and what that tells us about the way the infection spreads in the lung. In particular, they looked at the surface of the lung cells, because this is the part directly involved in the first contact with the Mycobacterium. As they report now in the international open-access medical journal PLoS Medicine, they studied 74 individuals, 40 of whom had TB, 25 had other inflammatory lung diseases, and 9 had neither active TB nor lung inflammation and served as healthy "controls." The patients underwent a procedure called broncho-alveolar lavage that washes out some of the secretions and cells from the lower respiratory tract. The researchers then analyzed the cells in different ways. They concentrated on a type of cell called a macrophage (the natural target of Mycobacterium) and found that macrophages from patients with TB had much more the DC-SIGN protein on their surface than macrophages from patients with other diseases or from the control individuals.

They then took macrophages from a control individual (which had very low levels of DC-SIGN) and infected them with Mycobaterium under laboratory conditions. They found that shortly after infection not only the infected cells but also some of their neighbours started to display DC-SIGN on their surface. They also found that having DC-SIGN on the surface made uninfected cells much more susceptible to infection.

These results suggest that DC-SIGN has an important function in amplifying TB infection in the lung. Interfering with DC-SIGN function might therefore be a new way to fight TB, a disease that is becoming increasingly resistant to existing therapies and for which new drugs are urgently needed.

Source : Public Library of Science