Sepsis Triggers a Late Expansion of Functionally Impaired Tissue-Vascular Inflammatory Monocytes During Clinical...

Area of Science:

• Immunology
• Infectious Diseases
• Critical Care Medicine

Background:

• Sepsis involves systemic inflammation and immune dysfunction with unclear mechanisms.
• Monocyte (Mo) mobilization and function are critical in sepsis pathogenesis and recovery.

Purpose of the Study:

• To investigate the impact of cecal ligature and puncture (CLP)-induced sepsis on monocyte mobilization and functions.
• To elucidate the role of monocytes in sepsis-induced immune dysfunction and susceptibility to secondary infections.

Main Methods:

• Induction of polymicrobial sepsis using cecal ligature and puncture (CLP) in a mouse model.
• Analysis of monocyte mobilization, distribution, and function during different phases of sepsis and recovery.
• Assessment of monocyte protective capacity against secondary infections in CCR2-deficient mice.

Main Results:

• CLP-induced sepsis resulted in two distinct phases of monocyte deployment, with a prolonged second phase after apparent recovery.
• Expanded monocytes accumulated in vascular tissues, exhibiting impaired activation and phagocytic functions.
• Intravascular monocytes failed to provide protection against secondary infections, even in the absence of overt clinical symptoms.

Conclusions:

• Sepsis recovery is characterized by dysfunctional intravascular monocytes, compromising host defense.
• These findings highlight critical immune deficits during sepsis recovery, offering targets for improved patient management and protection against secondary infections.