CD14 recycling modulates LPS‐induced inflammatory responses of murine macrophages

• DOI: 10.1111/tra.12842
• Publication Date: 2022-04-12T07:37:43Z
• Authors: Anna Ciesielska; Marta Krawczyk; Hanna Sas‐Nowosie...; Aneta Hromada‐Jud...; Katarzyna Kwiatko...
• Keywords: Proinflammatory cytokine; TRIF

Abstract TLR4 is activated by the bacterial endotoxin lipopolysaccharide (LPS) and triggers two proinflammatory signaling cascades: a MyD88‐dependent one in plasma membrane, following TRIF‐dependent endosomes. An inadequate inflammatory reaction can be detrimental for organism leading to sepsis. Therefore, novel approaches therapeutic modulation of are being sought after. The activity tightly connected with presence CD14, GPI‐anchored protein that transfers LPS monomers receptor controls its endocytosis. In this study we focused on CD14 trafficking as still poorly understood factor affecting activity. Two independent assays were used show after endocytosis recycle back membrane both unstimulated stimulated cells. This route controlled sorting nexins (SNX) 1, 2 6, important maintaining surface level total but also affect amount TLR4. Silencing these SNXs attenuated especially CD14‐dependent endosomal TLR4, making them new target regulation response macrophages LPS.