Abstract
Macrophages predominate the inflammatory landscape within multiple sclerosis (MS) lesions, not only regarding cellularity but also with respect to the diverse functions this cell fraction provides during disease progression and remission. Researchers have been well aware of the fact that the macrophage pool during central nervous system (CNS) autoimmunity consists of a mixture of myeloid cells. Yet, separating these populations to define their unique contribution to disease pathology has long been challenging due to their similar marker expression. Sophisticated lineage tracing approaches as well as comprehensive transcriptome analysis have elevated our insight into macrophage biology to a new level enabling scientists to dissect the roles of resident (microglia and non-parenchymal macrophages) and infiltrating macrophages with unprecedented precision. To do so in an accurate way, researchers have to know their toolbox, which has been filled with diverse, discriminating approaches from decades of studying neuroinflammation in animal models. Every method has its own strengths and weaknesses, which will be addressed in this review. The focus will be on tools to manipulate and/or identify different macrophage subgroups within the injured murine CNS.
Highlights
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS) characterized by focal lesions of inflammation, demyelination, gliosis and axonal loss [1]
It is acknowledged that cell shape cannot be used as a criterion to distinguish these two populations in CNS inflammation. While this might be true for conventional light microscopy applications, successful discrimination between microglia and monocyte-derived macrophages has been reported in EAE using serial block face scanning electron microscopy (SBF-EM) [41]
The ablated bone marrow (BM) of the recipient is populated by physiologically circulating hematopoietic stem cells (HSCs) from the donor [96,97], which has been shielded from irradiation
Summary
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS) characterized by focal lesions of inflammation, demyelination, gliosis and axonal loss [1]. Sophisticated lineage tracing approaches as well as comprehensive transcriptome analysis have significantly advanced our knowledge on macrophage diversity over the last years, substantiating the notion that infiltrating and resident CNS macrophages are two separate entities with specialized functions and behaviors [13,14,15,16]. They have given us a better understanding of the heterogeneity of myeloid cells within the CNS [17]. We would like to discuss such novel as well as traditional approaches, while focusing on methods to genetically manipulate and/or identify infiltrating and resident macrophage populations in EAE
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