Journal
NATURE NEUROSCIENCE
Volume 14, Issue 9, Pages 1142-U263Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.2887
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Funding
- Canadian Institute for Health Research (CIHR) [MOP 81382]
- Multiple Sclerosis Society of Canada
- Amyotrophic Lateral Sclerosis Society of Canada
- Muscular Dystrophy Canada [JNM-69682]
- Natural Science and Engineering Research Council of Canada [CHRP 299119]
- Michael Smith Foundation for Health Research Senior Scholar
- Michael Smith Foundation
- Canadian Research Chairs program
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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.
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