Macrophages (CD68s)

Macrophages are the most important phagocytes in vivo (6). They undergo profound metabolic reprogramming upon sensing infectious and sterile stimuli (3). Macrophages respond to their environment and become activated. They then produce cytokines that affect the biology of other cells. This process can be influenced by the direct action of danger signals and cytokines produced by different cell types, immune and non-immune. Physiologically, they are crucial: eliminating microbial infections and dead cells, initiation and resolution of inflammation, and tissue homeostasis (8). Interleukin-3 (IL-3) and Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate production of new macrophages.

Nearly all tissues are populated by self-maintaining pools of tissue-resident macrophages (RTMs). A third classic example of this core macrophage function is the role that different tissue-resident macrophages (RTMs) play while clearing cellular nuclei and debris during the development and subsequent clearance of other immune cells. Early studies have shown that macrophages interact with neurons in the central and peripheral nervous systems (CNS and PNS) (5)

To maintain and regulate intestinal homeostasis, the gut is equipped with one of the largest populations of macrophages in the body (1). Experiments in mice have shown that Intestinal mucosal macrophages are continuously replenished by peripheral monocytes in a CCR2-dependent manner (2).

The two main inflammatory phenotypes of macrophages, M1 macrophages (CD68+ iNOS+) and M2 macrophages (CD68+ CD163+), are controlled by differential consumption of glucose, glutamine, and oxygen (7). However, macrophage polarization represents a continuum in which the macrophage population will show a mixture of M1 and M2 phenotypes as well as macrophages in a transition state expressing markers of both M1 and M2 phenotypes. As such, a balance in macrophage phenotypes plays a key role in homeostasis and pathogenicity (4)

References:

(1) Delfini et al. 2022 Immunity 55(9): 1530-1548
(2) Bain et al. 2014 Nat Immunol 15: 929-937
(3) Olona et al. 2022 Trends in Immunology 43(12): 978
(4) Fuchs & Trauner 2022 Nat Rev Gastroenterol Hepatol 19: 432-450
(5) Park et al. 2022a Cell 185: 4259-4279
(6) Li et al. 2021a
(7) Belizario et al. 2018
(8) Wynn et al. 2013 Nature 496(7446): 445-455

see also:
Activation / Activators & Macrophages
Immune cell metabolism / Immunometabolism