Peferoen LA, Vogel DY, Ummenthum K, Breur M, Heijnen PD, Gerritsen WH, Peferoen-Baert RM, van der Valk P, Dijkstra CD, Amor S. Activation Status of Human Microglia Is Dependent on Lesion Formation Stage and Remyelination in Multiple Sclerosis. J Neuropathol Exp Neurol. 2014 Dec. [Epub ahead of print]
Similar to macrophages, microglia adopt diverse activation states and contribute to repair and tissue damage in multiple sclerosis. Using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, we show that in vitro M1-polarized (proinflammatory) human adult microglia express the distinctive markers CD74, CD40, CD86, and CCR7, whereas M2 (anti-inflammatory) microglia express mannose receptor and the anti-inflammatory cytokine CCL22. The expression of these markers was assessed in clusters of activated microglia in normal-appearing white matter (preactive lesions) and areas of remyelination, representing reparative multiple sclerosis lesions. We show that activated microglia in preactive and remyelinating lesions express CD74, CD40, CD86, and the M2 markers CCL22 and CD209, but not mannose receptor. To examine whether this intermediate microglia profile is static or dynamic and thus susceptible to changes in the microenvironment, we polarized microglia into M1 or M2 phenotype in vitro and then subsequently treated them with the opposing polarization regimen. These studies revealed that expression of CD40, CXCL10, and mannose receptor is dynamic and that microglia, like macrophages, can switch between M1 and M2 phenotypic profiles. Taken together, our data define the differential activation states of microglia during lesion development in multiple sclerosis-affected CNS tissues and underscore the plasticity of human adult microglia in vitro.
Some people think microglial are good guys that cause repair and macrophages are bad guys, but this study suggests they can be both good and bad. Just as T cells have been pigeon holed into TH1 (bad) and TH2 (good) guys. This formed the treatment ideas for many a drug. However, this distinction is less clear cut in humans and is driving a TH2 response a good thing? I suspect neither a TH1 or TH2 is a good idea. In this study they suggest that the microglia is fluid in that they can become M1 and M2 microglia and that the cells in the CNS may be not quite an one or the other in the cells forming lesion or repair.
CoI DoctorLove is part of TeamG