Abstract
Inflammation is a series of processes designed for eventual clearance of pathogens and repair of damaged tissue. In the context of autoimmune recognition, inflammatory processes are usually considered to be pathological. This is also true for inflammatory responses in the central nervous system (CNS). However, as in other tissues, neuroinflammation can have beneficial as well as pathological outcomes. The complex role of encephalitogenic T cells in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE) may derive from heterogeneity of the myeloid cells with which these T cells interact within the CNS. Myeloid cells, including resident microglia and infiltrating bone marrow-derived cells, such as dendritic cells (DC) and monocytes/macrophages [bone marrow-derived macrophages (BMDM)], are highly heterogeneous populations that may be involved in neurotoxicity and also immunoregulation and regenerative processes. Better understanding and characterization of myeloid cell heterogeneity is essential for future development of treatments controlling inflammation and inducing neuroprotection and neuroregeneration in diseased CNS. Here, we describe and compare three populations of myeloid cells: CD11c+ microglia, CD11c− microglia, and CD11c+ blood-derived cells in terms of their pathological versus protective functions in the CNS of mice with EAE. Our data show that CNS-resident microglia include functionally distinct subsets that can be distinguished by their expression of CD11c. These subsets differ in their expression of Arg-1, YM1, iNOS, IL-10, and IGF-1. Moreover, in contrast to BMDM/DC, both subsets of microglia express protective interferon-beta (IFNβ), high levels of colony-stimulating factor-1 receptor, and do not express the Th1-associated transcription factor T-bet. Taken together, our data suggest that CD11c+ microglia, CD11c− microglia, and infiltrating BMDM/DC represent separate and distinct populations and illustrate the heterogeneity of the CNS inflammatory environment.
Highlights
The contribution of myeloid cells to central nervous system (CNS) function is increasingly appreciated
Over two decades of research on CD4+ T cell subsets based on their cytokine production profile has led to major increases in understanding of the inflammatory process
Summary
The contribution of myeloid cells to central nervous system (CNS) function is increasingly appreciated. A key aspect of the inflammatory response within the CNS is the recruitment and reactivation of infiltrating CD4+ T cells and direction of their effector function within the tissue [2]. Their role in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) is complex. The cells implicated in interaction with CD4+ T cells within the inflamed CNS are myeloid cells, such as infiltrating dendritic cells (DC) and monocytes/macrophages, and resident microglia [6,7,8,9] These are very heterogeneous populations of immune cells that can dampen inflammation or contribute to pathological events.
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