72
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Microglia and monocyte-derived macrophages: functionally distinct populations that act in concert in CNS plasticity and repair

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Functional macrophage heterogeneity is recognized outside the central nervous system (CNS), where alternatively activated macrophages can perform immune-resolving functions. Such functional heterogeneity was largely ignored in the CNS, with respect to the resident microglia and the myeloid-derived cells recruited from the blood following injury or disease, previously defined as blood-derived microglia; both were indistinguishably perceived detrimental. Our studies have led us to view the myeloid-derived infiltrating cells as functionally distinct from the resident microglia, and accordingly, to name them monocyte-derived macrophages (mo-MΦ). Although microglia perform various maintenance and protective roles, under certain conditions when they can no longer provide protection, mo-MΦ are recruited to the damaged CNS; there, they act not as microglial replacements but rather assistant cells, providing activities that cannot be timely performed by the resident cells. Here, we focus on the functional heterogeneity of microglia/mo-MΦ, emphasizing that, as opposed to the mo-MΦ, microglia often fail to timely acquire the phenotype essential for CNS repair.

          Related collections

          Most cited references87

          • Record: found
          • Abstract: found
          • Article: not found

          Local self-renewal can sustain CNS microglia maintenance and function throughout adult life.

          Microgliosis is a common response to multiple types of damage in the CNS. However, the origin of the cells involved in this process is still controversial and the relative importance of local expansion versus recruitment of microglia progenitors from the bloodstream is unclear. Here, we investigated the origin of microglia using chimeric animals obtained by parabiosis. We found no evidence of microglia progenitor recruitment from the circulation in denervation or CNS neurodegenerative disease, suggesting that maintenance and local expansion of microglia are solely dependent on the self-renewal of CNS resident cells in these models.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism.

            Inflammation, a common denominator among the diverse list of neurodegenerative diseases, has recently been implicated as a critical mechanism responsible for the progressive nature of neurodegeneration. Microglia are the resident innate immune cells in the central nervous system and produce a barrage of factors (IL-1, TNFalpha, NO, PGE2, superoxide) that are toxic to neurons. Evidence supports that the unregulated activation of microglia in response to environmental toxins, endogenous proteins, and neuronal death results in the production of toxic factors that propagate neuronal injury. In the following review, we discuss the common thread of microglial activation across numerous neurodegenerative diseases, define current perceptions of how microglia are damaging neurons, and explain how the microglial response to neuronal damage results in a self-propelling cycle of neuron death.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool.

              In multiple sclerosis and the experimental autoimmune encephalitis (EAE) mouse model, two pools of morphologically indistinguishable phagocytic cells, microglia and inflammatory macrophages, accrue from proliferating resident precursors and recruitment of blood-borne progenitors, respectively. Whether these cell types are functionally equivalent is hotly debated, but is challenging to address experimentally. Using a combination of parabiosis and myeloablation to replace circulating progenitors without affecting CNS-resident microglia, we found a strong correlation between monocyte infiltration and progression to the paralytic stage of EAE. Inhibition of chemokine receptor-dependent recruitment of monocytes to the CNS blocked EAE progression, suggesting that these infiltrating cells are essential for pathogenesis. Finally, we found that, although microglia can enter the cell cycle and return to quiescence following remission, recruited monocytes vanish, and therefore do not ultimately contribute to the resident microglial pool. In conclusion, we identified two distinct subsets of myelomonocytic cells with distinct roles in neuroinflammation and disease progression.
                Bookmark

                Author and article information

                Journal
                Front Cell Neurosci
                Front Cell Neurosci
                Front. Cell. Neurosci.
                Frontiers in Cellular Neuroscience
                Frontiers Media S.A.
                1662-5102
                08 April 2013
                2013
                : 7
                : 34
                Affiliations
                Department of Neurobiology, Weizmann Institute of Science Rehovot, Israel
                Author notes

                Edited by: Amanda Sierra, Ikerbasque Foundation, University of the Basque Country EHU/UPV, Spain

                Reviewed by: Shaoyu Ge, State University of New York at Stony Brook, USA; Monica J. Carson, University of California, Riverside, USA

                *Correspondence: Michal Schwartz, Department of Neurobiology, Weizmann Institute of Science, P. O. Box 26, Rehovot 76100, Israel. e-mail: michal.schwartz@ 123456weizmann.ac.il
                Article
                10.3389/fncel.2013.00034
                3625831
                23596391
                bbcca9bf-c243-4ef2-bf0e-2e6a54349116
                Copyright © London, Cohen and Schwartz.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 30 January 2013
                : 18 March 2013
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 138, Pages: 10, Words: 0
                Categories
                Neuroscience
                Hypothesis & Theory

                Neurosciences
                microglia,monocytes,cns,innate,resolution of inflammation,macrophages,neuroprotection,monocyte-derived macrophages

                Comments

                Comment on this article