Single-cell mass cytometry reveals distinct populations of brain myeloid cells in mouse neuroinflammation and neurodegeneration models

Neuroinflammation and neurodegeneration may represent two polarities of brain pathology. Brain myeloid cells, particularly microglia, play key roles in these conditions. Here, we employed single-cell mass cytometry (CyToF) to compare myeloid cell populations in the experimental autoimmune encephalomyelitis (EAE) model of neuroinflammation, the R6/2 model of Huntington’s disease (HD), and the superoxide dismutase 1 (mSOD1) model of amyotrophic lateral sclerosis (ALS). We identified three myeloid cell populations exclusive to the central nervous system (CNS) and present in each disease model. Blood-derived monocytes comprised five populations and migrated to the brain in EAE, but not in HD and ALS models. Single-cell analysis resolved differences in signaling and cytokine production within similar myeloid populations in EAE compared to HD and ALS models. Moreover, these analyses highlighted α5 integrin on myeloid cells as a potential therapeutic target for neuroinflammation. Together, these findings illustrate how neuropathology may differ between inflammatory and degenerative brain disease.