toxic mediators, including reactive species, and contribute to CNS
damage). But what makes these differences. In this beautiful study we find that it is environment within the CNS that dictates the path they choose.
Locatelli G, Theodorou D, Kendirli A, Jordão MJC, Staszewski O, Phulphagar K, Cantuti-Castelvetri L, Dagkalis A, Bessis A, Simons M, Meissner F, Prinz M, Kerschensteiner M.Mononuclear phagocytes locally specify and adapt their phenotype in a multiple sclerosis model. Nat Neurosci. 2018;21(9):1196-1208.
In this study they established a phenotype imaging approach based on reporter mice that translate the pro- or anti-inflammatory polarization of phagocytes (M1 or M2) into distinct fluorescent signals.
Imaging of these in real time in an animal model of MS then allowed them to follow the evolution of individual phagocyte types in different CNS compartments during the formation and resolution of inflammatory lesions.
There results show that both lesion stage and CNS compartment influenced the phagocyte polarization in neuroinflammatory lesions.
Phagocytes that enter from the blood stream acquire their initial polarization only after spinal cord entry, and the nature of this polarization critically depends on the compartment they enter.
While phagocytes in the spinal cord parenchyma predominantly show an M1 polarization at the initial stages of lesion formation, phagocytes in the meninges often display an M2 phenotype.
Once in the CNS the M1 began a conversion to M2 rather than a new wave of infiltration of M2 cells. This was facilitated by the action of astrocytes. Phagocytes acquired their initial polarization after CNS entry, and, as the disease evolved, individual phagocytes locally switched their phenotype by passing through a transitional state. Therefore, suggesting that the natural effect of the CNS environment is to turn the bad guys into the good guys. This was associated with changes in biochemical function other than those associated with cytokine production. The critical instructive role of the CNS environment was further emphasized by cell transfers.
Therefore treatments aimied at switching M1 to M2 macrophages may not be needed, as it will happen anyway