Do not judge a cell by its cover—diversity of CNS resident, adjoining and infiltrating myeloid cells in inflammation

Specialized populations of tissue-resident myeloid cells inhabit every organ of the body. While many of these populations appear similar morphologically and phenotypically, they exhibit great functional diversity. The central nervous system (CNS), as an immune privileged organ, possesses a unique tissue-resident macrophage population, the microglia, as well as numerous myeloid cell subsets at its boarders and barriers in CNS-adjoining tissues, namely the meninges, the perivascular space, and the choroid plexus. Recent research has added much to our knowledge about microglia, whereas the populations of CNS-surrounding phagocytes are just starting to be appreciated. As guardians of CNS homeostasis, these myeloid cells perform immune surveillance and immune modulatory tasks in health and disease. As such, microglia and CNS-surrounding antigen-presenting cells have been shown to be crucially involved not only in the initiation and progression but also resolution of multiple sclerosis (MS). MS and its rodent model, experimental autoimmune encephalomyelitis, are autoimmune inflammatory demyelinating CNS pathologies. While some crucial aspects of the disease pathogenesis have been solved, much of the complex involvement and interplay of the innate immune compartment remains yet to be clarified. Here, we will discuss the current understanding of the scope of phenotypes and functions of myeloid cells involved in CNS neuroinflammation.