Fever-range temperature alters continual efferocytosis mediated by mouse proinflammatory macrophages

Area of Science:

• Immunology
• Cell Biology

Background:

• Fever modulates macrophage functions, impacting inflammation resolution.
• Effectorocytosis is crucial for returning the body to homeostasis.

Purpose of the Study:

• To investigate the effect of fever on macrophage efferocytosis.
• To understand the mechanisms by which fever influences macrophage-mediated clearance of apoptotic cells.

Main Methods:

• Primary mouse bone marrow-derived macrophages were stimulated to become pro-inflammatory.
• Macrophages were exposed to febrile temperature (39.5°C).
• Effectorocytosis, cell motility, Mer receptor expression, and ADAM17 activity were assessed.

Main Results:

• Febrile temperature decreased macrophage efferocytosis and cell motility.
• Upregulation of Adam17 and shedding of the Mer receptor were observed.
• ADAM17 inhibition did not fully restore efferocytosis, suggesting other mechanisms are involved.

Conclusions:

• Fever reduces the efferocytic capacity of pro-inflammatory macrophages.
• This impairment may contribute to maintaining a pro-inflammatory state during fever.
• The study highlights a novel mechanism by which fever impacts immune resolution.