Can we protect ourselves from bacterial infections by changing our body's energy metabolism, especially from infections that are dependent on that? This is the question that Giuseppe Matarese et al asked themselves in their newest research in Cell Metabolism. In their newest research, they show that (healthy) caloric restriction can protect mice from pulmonary Mycobacterium tuberculosis (MTB) infection. Caloric restriction enhances the killing of MTB and it reduces the bacterial load in the lungs. Mechanistically, they discovered that caloric restriction induces immunometabolic reprogramming, a hallmark of trained immunity.
Healthy caloric restriction and its effect on MTB infection
In an elegant mouse study in vivo, Carla Palma and her co-workers show that healthy caloric restriction reduces MTB infection. Mice were challenged with MTB, after which they were either subjected to ad libitum feeding (which means as much as 'free food for all') or caloric restriction not leading to malnutrition (CR). The mice that were subjected to CR showed a significantly lower MTB load in their lungs, less granulomas, increased MTB killing and less inflammatory cytokines and neutrophil infiltration. (Figure below)
Source: Cell Metabolism
Mechanistically, the authors show that CR leads to trained immunity, resulting in immunometabolic reprogramming, a switch to glycolysis and a decrease in fatty acid oxidation and less activation of the mTOR pathway. Autophagy was increased as well as the P2rx7 purinertic receptor, all in all leading to the enhanced killing of MTB and also a reduction of collateral damage from the infection.
Interested to read more? You can find the paper here.
All other publications on trained immunity can be found here.