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bioRxiv · 10.64898/2026.09.16.751725

CX3CR1+ microglia/macrophages, activated T cells, and IFN-γ-driven stimulation confer age-dependent protective immunity in young-adult mice following β-coronavirus infection.

Ghosh, S.·Hazra, B.·Das Sarma, S.·Chakravarty, D.·DasSarma, J.
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Abstract

Age-dependent variation in the immune response is a critical determinant of host susceptibility, disease severity, and long-term sequelae in coronavirus infections, a principle strikingly demonstrated by the COVID-19 pandemic caused by SARS-CoV-2. Although primarily pneumotropic, coronaviruses carry significant neurotropic potential, driving neurological complications whose severity is profoundly determined by host age. Elderly individuals and often children suffer disproportionately severe disease, whereas young adults relatively mount protective responses; yet the cellular and molecular determinants of this age-dependent neuroprotection remain poorly characterized. Using juvenile and young-adult C57BL/6 mice intracranially inoculated with {beta}-coronavirus MHV-RSA59, a murine equivalent of human coronaviruses, we examined immune dynamics at days 5 (innate-acute), 7 (innate-to-adaptive transition), and 30 (chronic) post-infection. Young-adult mice exhibited only occasional demyelination, in stark contrast to the extensive demyelination observed across all spinal cord levels in juveniles. This differential outcome was attributable to enhanced age-dependent immune maturation, characterized by efficient T cell-microglia/macrophage crosstalk enabling effective viral control by day 7 post-infection. Young adults displayed greater glial activation, heightened cytokine release, CX3CR1+ microglia activation, and augmented CNS trafficking of CX3CR1+ and MHC II+ monocytes/macrophages, IFN-{gamma}+ CD4+/CD8+ T cells, and CXCR3+ effector T cells relative to juveniles. Reduced naive T cell frequencies and elevated effector/central memory T cell populations in cervical lymph nodes further indicate a robust adaptive memory response conferring long-term protection. Additionally, greater regulatory T cell accumulation in young adults facilitates timely suppression of excessive neuroinflammation as viral burden subsides. Together, these findings define the age-dependent immune landscape that underpins neuroprotection in {beta}-coronavirus infection.

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Ghosh, S., Hazra, B., Das Sarma, S., Chakravarty, D., DasSarma, J.. 2026-09-18. CX3CR1+ microglia/macrophages, activated T cells, and IFN-γ-driven stimulation confer age-dependent protective immunity in young-adult mice following β-coronavirus infection.. https://doi.org/10.64898/2026.09.16.751725

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