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bioRxiv · 10.1101/2022.06.10.495612

Microglia and meningeal macrophages depletion delay the onset of experimental autoimmune encephalomyelitis

Montilla, A.·Zabala, A.·Er-Lukowiak, M.·Rissiek, B.·Magnus, T.·Rodriguez-Iglesias, N.·Sierra, A.·Matute, C.·Domercq, M.
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Abstract

In multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, both resident microglia and infiltrating macrophages contribute to demyelination as well as spontaneous remyelination. Nevertheless, the specific roles of microglia versus macrophages are unknown. We investigated the influence of microglia in EAE using the colony stimulating factor 1 receptor (CSF-1R) inhibitor, PLX5622, to deplete microglial population and Ccr2RFP/+fmsEGFP/+ mice, to distinguish peripheral macrophages and microglia. PLX5622 treatment depleted microglia and meningeal macrophages, and provoked a massive infiltration of CCR2+ macrophages into demyelinating lesions and spinal cord parenchyma. PLX5622 treatment did not alter EAE chronic phase. In contrast, microglia and meningeal macrophages depletion reduced the expression of CD80 co-stimulatory molecule in dendritic and myeloid cells and reduced T cell reactivation and proliferation in the spinal cord parenchyma, inducing a significant delay in EAE onset. Altogether, these data points to a specific role of CNS microglia meningeal macrophages in antigen presentation and T cell reactivation at initial stages of the EAE model.

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Montilla, A., Zabala, A., Er-Lukowiak, M., Rissiek, B., Magnus, T., Rodriguez-Iglesias, N., Sierra, A., Matute, C., Domercq, M.. 2022-06-12. Microglia and meningeal macrophages depletion delay the onset of experimental autoimmune encephalomyelitis. https://doi.org/10.1101/2022.06.10.495612

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