Role of monocyte-derived macrophages in critically ill patients

Critical illness, a state of health instability and organ dysfunction necessitating urgent medical attention, is often characterized by dysregulated immune responses, which can counterintuitively lead to immunosuppression. As such, critically ill patients are at high risk of secondary infections and a prolonged unstable health status. Monocyte-derived macrophages (MDMs) are tissue-resident innate immune cells originating from circulating monocytes. MDMs play a crucial role in orchestrating immune responses in critical illnesses and can differentiate into an inflammatory (M1) or anti-inflammatory (M2) state dictated by the tissue status where they migrate. MDMs are responsible for maintaining tissue homeostasis by performing phagocytosis and pathogen clearance, functions that are dependent on their inflammatory state. In this study, I investigated the phagocytosis and bacteria-killing function of MDMs derived from the peripheral blood of healthy donors and critically ill patients. Moreover, I aimed to understand alterations in the functionality of these MDMs following lipopolysaccharide (LPS) treatment in both health and critical illness. This study revealed that LPS treatment causes decreased phagocytosis and bacteria killing in health and critical illness, indicating an induced tolerance in most critically ill patients. Moreover, LPS re-stimulated inflammatory (M1) MDMs demonstrated a reduction in the phagocytosis index of most critically ill patients. The findings suggest that most MDM responses are similar in health and critical illness, with reduced MDMs’ responses after LPS restimulation demonstrating an induced immune tolerance in health and critical illness.