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Published on: October 6, 2023
Persistence of apoptotic cells without autoimmune disease or inflammation in CD14-/- mice
Andrew Devitt1, Kate G Parker, Carol Anne Ogden
1Medical Research Council Centre for Inflammation Research, University of Edinburgh, Edinburgh, Scotland, UK.
Abstract:
Interaction of macrophages with apoptotic cells involves multiple steps including recognition, tethering, phagocytosis, and anti-inflammatory macrophage responses. Defective apoptotic cell clearance is associated with pathogenesis of autoimmune disease. CD14 is a surface receptor that functions in vitro in the removal of apoptotic cells by human and murine macrophages, but its mechanism of action has not been defined. Here, we demonstrate that CD14 functions as a macrophage tethering receptor for apoptotic cells. Significantly, CD14(-/-) macrophages in vivo are defective in clearing apoptotic cells in multiple tissues, suggesting a broad role for CD14 in the clearance process. However, the resultant persistence of apoptotic cells does not lead to inflammation or increased autoantibody production, most likely because, as we show, CD14(-/-) macrophages retain the ability to generate anti-inflammatory signals in response to apoptotic cells. We conclude that CD14 plays a broad tethering role in apoptotic cell clearance in vivo and that apoptotic cells can persist in the absence of proinflammatory consequences.
Insights
CD14 acts as a crucial tethering receptor for macrophages to bind apoptotic cells. While CD14-deficient macrophages struggle with clearance in vivo, they still prevent inflammation, highlighting a complex role in immune response.
Area of Science:
- Immunology
- Cell Biology
Background:
- Defective clearance of apoptotic cells is linked to autoimmune disease pathogenesis.
- CD14 is a known macrophage surface receptor involved in apoptotic cell removal, but its precise mechanism remains unclear.
Purpose of the Study:
- To elucidate the mechanism by which CD14 mediates the removal of apoptotic cells by macrophages.
- To investigate the in vivo role of CD14 in apoptotic cell clearance and its consequences.
Main Methods:
- Utilized CD14-deficient (CD14(-/-)) macrophages in in vitro and in vivo models.
- Assessed macrophage interaction, apoptotic cell clearance, inflammatory responses, and autoantibody production in CD14(-/-) models.
Main Results:
- Demonstrated that CD14 functions as a macrophage tethering receptor for apoptotic cells.
- Showed CD14(-/-) macrophages exhibit impaired in vivo clearance of apoptotic cells across multiple tissues.
- Observed that persistent apoptotic cells in CD14(-/-) mice did not induce inflammation or autoantibody production, as anti-inflammatory signals were retained.
Conclusions:
- CD14 plays a significant, broad tethering role in the in vivo clearance of apoptotic cells.
- Apoptotic cell persistence, even without efficient clearance mediated by CD14, does not necessarily lead to pro-inflammatory outcomes.
