The changing phenotype of microglia from homeostasis to disease

Luo, Xiao-Guang; Chen, Sheng-Di

The entire immune response consists of the cooperation of the innate and adaptive immune systems. In the brain, it has been postulated that the beneficial or destructive outcome of the local microglial (innate) response is determined by a well-controlled dialogue between the innate and the adaptive immune players, which are, in most cases, the microglia and T cells. Activated T cells can cross the bloodbrain barrier and interact with resident microglia in the parenchyma [130] ; these microglia have been characterized as myeloid progenitor cells that can differentiate into macrophage-like or dendritic-like cells [131] and thus work crucially as the principal APCs [85] in the CNS. Monsonego et al. demonstrated that IFN-γ-treated microglia serve as efficient Aβ antigen-presenting cells (APCs) of both Aβ1-40 and Aβ1-42, mediating CD86-dependent proliferation of Aβ-reactive T cells [132] . The activated T cells then exert effects in the injured neural tissues by altering the reactive microglial phenotypes and inducing the astrocytic expression of growth factors or modulating microglia to act as glutamate scavengers [44] to improve neuronal survival [133, 134] . In a model for optic nerve injury, the passive transfer of regulatory CD4 + CD25+ T cells was either destructive or beneficial depending on the genetic background of the mice tested, which determines the differential interaction of T cells with microglia and thus the different T cellmediated microglial phenotypes [133] . Kipnis even observed that both the suppressor and the effector activities of T cells could be mediated through dialogue with microglia in the condition of neurodegneration [135] , The entire scenario of crosstalk between T cells and microglia could be described as the following: microglia are initially activated by pathological stimuli during acute or chronic injury to the brain; if the activation occurs with the proper timing and mode and is well-controlled, the activated microglia will work as APCs [133] to stimulate Treg cells that eventually modulate the microglial activation directly or indirectly and affect the milieu balance between neurotrophism and cytotoxicity [44, 136, 137] .