New therapeutic target in sepsis

Netea Mihai 2014

During the late phase of very severe systemic infections (also called sepsis), the host defense of the patients is unable to fight the invading pathogens, leading to increasingly severe diseases as well as repeated secondary infections. This phase of sepsis is characterized thus by so-called immune paralysis, and is responsible for a large proportions of deaths in this very severe condition. The mechanisms responsible for the immune paralysis in sepsis are poorly known.

In a collaborative study between the groups of Mihai Netea, Dept. of Internal Medicine, Theme Infectious diseases and global health and Tom van der Poll (AMC), an important piece to decipher the mechanisms responsible for sepsis has been unraveled. It turns out that during sepsis the monocytes, important immune cells for host defense, suffer for the incapacity to metabolize energy substrates. This de facto immunometabolic paralysis leads to defects of the energy stores in the immune cells, which are incapable to exert their function in host defense. The researchers were also able to identify interferon-gamma as a potential treatment that partially restores this defect. It is hoped that identification of this important pathway responsible for the immune defects in sepsis will lead to even more effective therapies to restore host defense in sepsis patients and improve their survival.


Broad defects in energy metabolism of leukocytes underlie immunoparalysis in sepsis. Nature Immunology, 2016



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