Metabolic reprogramming and dysregulated IL-17 production impairs CD4 T cell function post sepsis

Area of Science:

• Immunology
• Cellular Metabolism
• Infectious Disease

Background:

• Sepsis survivors face increased risk of infection-related rehospitalization and mortality.
• Compromised immune responses in sepsis survivors suggest impaired T cell function.
• CD4 T cells are crucial for developing long-lasting protective immunity.

Purpose of the Study:

• To investigate the post-septic function of CD4 T cells.
• To identify the mechanisms underlying immune dysfunction in sepsis survivors.
• To explore potential therapeutic targets for mitigating secondary infections in sepsis survivors.

Main Methods:

• Analysis of CD4 T cell function in a sepsis model.
• Measurement of cytokine production, including IL-17.
• Assessment of cellular metabolism, including mitochondrial function and glycolysis.
• Evaluation of immune response to secondary pneumonia challenge.

Main Results:

• Sepsis induced chronic, increased, and non-specific IL-17 production by CD4 T cells.
• This altered T cell function impaired the immune response to secondary pneumonia.
• Cellular metabolic reprogramming, including mitochondrial dysfunction and increased glycolysis, was observed.
• Metabolic changes initiated during acute sepsis persisted long after resolution.

Conclusions:

• Chronic IL-17 overproduction by CD4 T cells contributes to immune deficiency in sepsis survivors.
• Cellular metabolic reprogramming is a key feature of post-septic immune dysfunction.
• Targeting cell metabolism offers a potential therapeutic strategy to improve outcomes for sepsis survivors.