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. 2021 Apr 14;22(8):4039. doi: 10.3390/ijms22084039

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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The lipid-laden macrophage. 1. Lipid cargo enters macrophages through uptake by scavenger receptors (CD36, TREM-2), or via phagocytosis of red blood cells, or apoptotic cells. 2. Captured lipids will be broken down in lysosomes. Due to defects in the catabolic machinery (GD, or NPC), or due to acquired overload (myelin, TG, or oxLDL) lipid material will be stored in 3. droplets/lysosome. 4. Transcriptional regulation a. MiT-TFE driven lysosomal biogenesis and autophagy and b. M1 phenotype suppression (LXR/PPARγ). Induction of p62, occurring as a consequence of autophagy inhibition also contributes to immune suppression.