Abstract
Although aggravated multiple sclerosis (MS) disability has been reported in aged patients, the aging impact on immune cells remodeling within the CNS is not well understood. Here, we investigated the influence of aging on immune cells and the neuroinflammatory and neurodegenerative processes that occur in a well‐established viral model of progressive MS. We found an anomalous presence of CD4+ T, CD8+T, B cells, and cells of myeloid lineage in the CNS of old sham mice whereas a blunted cellular innate and adaptive immune response was observed in Theiler's murine encephalomyelitis virus (TMEV) infected old mice. Microglia and macrophages show opposite CNS viral responses regarding cell counts in the old mice. Furthermore, enhanced expression of Programmed Death‐ligand 1 (PD‐L1) was found in microglia isolated from old TMEV‐infected mice and not in isolated CNS macrophages. Immunocytochemical staining of microglial cells confirms the above differences between young and old mice. Age‐related axonal loss integrity in the mouse spinal cord was found in TMEV mice, but a less marked neurodegenerative process was present in old sham mice compared with young sham mice. TMEV and sham old mice also display alterations in innate and adaptive immunity in the spleen compared to the young mice. Our study supports the need of new or adapted pharmacological strategies for MS elderly patients.
Highlights
Multiple sclerosis (MS) is a chronic inflammatory demyelinating CNS disease characterized by reversible neurological deficits associated with inflammation and secondary progressive neurodegeneration.About 80% of multiple sclerosis (MS) patients are diagnosed with the relapsing- remitting form (RRMS), but 70% of these patients shift to a progressive disease course (PMS) as they age (Tutuncú et al, 2013)
Theiler's murine encephalomyelitis virus (TMEV)-IDD model features a chronic progressive disease course which lasts for the entire lifespan in susceptible mice showing a dynamic of motor dysfunction and score severity that depends on the virus strain (McCarthy et al, 2012)
In the viral model used here, the brain cellular remodeling that occurs in adaptive immunity as mice get old reflects a blunted TMEV immune response, being largely a consequence of the changes observed in the old control mice that exhibited an anomalous presence of CD4+ and CD8+ T cells
Summary
About 80% of MS patients are diagnosed with the relapsing- remitting form (RRMS), but 70% of these patients shift to a progressive disease course (PMS) as they age (Tutuncú et al, 2013). This change has been related to immunosenescence, the changes that occur in the cellular immune response as a result of aging. Premature immune aging has been described in some MS patients, perhaps underlying the transition from the RR form to a progressive disease course (Thewissen et al, 2005). Interest in understanding the impact of aging on the course of MS has emerged in an attempt to find novel therapies or to adapt current treatments to the chronological age of patients (Vaughn et al, 2019)
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