Physiologic disruption and metabolic reprogramming in infection and sepsis

Area of Science:

• Immunology
• Infectious Diseases
• Metabolic Regulation

Background:

• Severe systemic infections necessitate a balance between resistance (pathogen elimination) and disease tolerance (limiting host damage).
• These defense strategies often involve distinct metabolic programs that may conflict.
• Evolutionary pressures initially favor resistance, potentially at the cost of disease tolerance and organ function.

Purpose of the Study:

• To review the role of physiological changes during infection in immune response.
• To outline the metabolic requirements for resistance and disease tolerance.
• To explore how understanding the interplay between these mechanisms can improve sepsis treatment.

Main Methods:

• Literature review and synthesis of current research on host-pathogen interactions.
• Analysis of metabolic reprogramming in the context of immune responses.
• Discussion of potential therapeutic targets and strategies.

Main Results:

• Resistance and disease tolerance are complementary but often conflicting immune strategies.
• Metabolic programs supporting resistance may impair disease tolerance, contributing to organ damage.
• Physiological perturbations during infection significantly influence immune dynamics.

Conclusions:

• Balancing resistance and disease tolerance is crucial for effective infection control and host survival.
• Targeting metabolic pathways could offer novel therapeutic interventions for sepsis.
• Further research into the interplay of these defense mechanisms is vital for improving clinical outcomes in severe infections.