The biological resilience of the tuberculosis causative agent (Mycobacterium tuberculosis) lies in its unique adaptive ability. The bacterium alters the body’s immune response to its own advantage and uses it for survival. A research team has made this process even clearer. It was discovered that the bacterium modifies the function of the Dectin-1 receptor, and as a result, instead of destroying the pathogen, the receptor facilitates its survival. Through this mechanism, the tuberculosis pathogen inhibits cellular self-cleansing and multiplies unhindered within macrophages.
The study showed that the bacterium uses a specific carbohydrate, Alpha-glucan, to purposefully bind to the Dectin-1 receptor. Under normal conditions, this contact should result in the destruction of the pathogen; however, in the case of tuberculosis, the process develops quite differently: the mTOR protein is activated, which halts the process of autophagy inside the cell.
In this way, the bacterium avoids lysosomal degradation and creates a favorable environment for survival within macrophages. Experimental models confirmed that when the Dectin-1 receptor is blocked, the bacterial load is reduced tenfold. These data once again confirm the decisive role of this receptor in the development of the infection.
The Role of Alpha-glucan
Structural analysis showed that the core of this mechanism is the bacterial branched Alpha-glucan. This finding was unexpected because the Dectin-1 receptor was previously considered a response mechanism only for fungal infections. The research revealed that the tuberculosis pathogen has evolutionarily acquired the ability to bind with this receptor to alter the host cell’s immune signaling.
These data lay the foundation for a completely new method of treatment: “Host-directed therapy.” Its essence lies in the fact that instead of acting directly on the pathogen – which is often resistant to antibiotics – we can restore the altered immune signaling of the host cell.
Source: Science Immunology
