Tuberculosis remains the most deadly infectious disease in the world, with over 1.5 million fatalities recorded each year. The main cause of death in infected individuals is an excessive immune reaction, which causes the progressive destruction of lung tissue. To decipher the molecular mechanisms of this intense inflammatory reaction, researchers1 became interested in a membrane protein located on dendritic cells, one category of the immune system cells. They first studied the mechanisms of the inflammatory reaction in mice that cannot express the DCIR protein, after having injected them with the tuberculosis bacillus.
The team observed that these mice then generated more interferon-gamma-producing T lymphocytes—interferon-gamma being a substance responsible for activating macrophages, the cells infected by the bacillus. Yet, whilst this cascade of reactions reduces the proliferation of the pathogen within the organism, it also increases inflammation at the level of the lungs, which deteriorate irremediably. These results are in line with previous research, which demonstrated that auto-immune diseases in healthy mice devoid of DCIR proteins tend to rise as these mice age. They strengthen the hypothesis that the receptors in question are targeted by molecules transmitted by the host upon an inflammatory reaction.
Taken together, the sum of these studies provides a glimpse of the possibility that the immune response could be controlled via chemical substances acting directly on DCIR receptors. It could therefore be possible to stimulate the immune reaction whenever it proves incapable of defeating a disease, or on the contrary slow down inflammation before it becomes uncontrollable.
PNAS, January 2017
Source : DCIR : une molécule qui régule l’immunité contre la tuberculose