Beyond nutritional immunity: immune-stressing challenges basic paradigms of immunometabolism and immunology Original paper

What was reviewed?

This review explored the concept of immune-stressing and its relationship with immunometabolism in pathogen defense. The paper discusses how the immune system exploits the vulnerabilities of proliferating pathogens by subjecting them to resource-limiting stress and damaging stress. The author expanded on the traditional concept of nutritional immunity, which restricts access to micronutrients, to include broader metabolic restrictions, specifically limiting glucose and oxygen while generating metabolic byproducts like reactive oxygen species (ROS), lactic acid, and heat. The review also emphasizes how these processes play a pivotal role in the host’s ability to fight infections, focusing on the role of immune cells in controlling pathogen proliferation, while immune cells themselves avoid these metabolic stresses.

Who was reviewed?

The review integrates findings from immunology, nutritional immunity, and immunometabolism across various pathogen-host interaction studies, including bacterial, viral, and parasitic infections. It does not focus on a specific patient cohort. Still, it provides insights from both clinical and experimental models, considering how immune cells respond to stress at the molecular level during infection. The author highlights how immune responses, especially from effector cells, can be modulated by metabolic and environmental stresses, impacting pathogen control and immune outcomes.

Most important findings

The central idea presented is that immune-stressing is an essential mechanism by which hosts restrict pathogens. The review identifies glucose deprivation, oxygen limitation, and the production of ROS as critical tools in this process. These stressors specifically target proliferating pathogens, making them more susceptible while immune cells avoid these stresses by limiting their own proliferation at infected sites. The review connects these findings to immunometabolism, which explores the impact of metabolic pathways on immune cell function. Macrophages and T-cells, particularly, adapt their metabolism to avoid excessive stress while maintaining pathogen control. In contrast, pathogens with high proliferative rates are highly vulnerable to these immune-induced metabolic stresses. This process is particularly evident in bacterial infections like tuberculosis, where restricted access to essential nutrients and byproducts like ROS significantly impair pathogen growth and survival.

Key implications

The review offers important insights for clinicians working on immunotherapy or infections like tuberculosis. By targeting metabolic pathways that control immune-stressing, clinicians may develop novel therapies to boost immune responses and limit pathogen survival. Understanding how metabolic regulation influences immune cell function and pathogen growth opens avenues for treatment strategies that involve metabolic reprogramming or the manipulation of nutrient availability. This research may also inform antioxidant therapy in infection control, focusing on how ROS generation can be balanced to enhance pathogen defense without harming immune cells.