Mycobacterium tuberculosis-induced oligodendrocyte apoptosis promotes astrocyte-mediated cell-in-cell formation and phagocytosis in tuberculous meningitis

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OBJECTIVE: To determine whether cell-in-cell (CIC) structures exist in tuberculous meningitis (TBM) and to explore their clinical significance. METHODS: Pathological brain biopsies from TBM patients were retrospectively analyzed using H&E and immunohistochemistry, with a focus on CIC structures. Multicolor immunofluorescence and in vitro coculture of astrocytes and oligodendrocytes were employed to explore CIC characteristics and underlying mechanisms. Flow cytometry was used to assess Bacillus Calmette-Guérin (BCG)-induced oligodendrocyte apoptosis. RESULTS: CIC structures (CICs) were identified in TBM brain tissues. Astrocytes were confirmed as target cells, while oligodendrocytes and neurons acted as effector cells. Astrocytes engulfed oligodendrocytes both in vivo and in vitro. BCG infection induced oligodendrocyte apoptosis and significantly enhanced CIC formation and phagocytosis. Pretreatment with staurosporine also promoted these processes. CICs observed in TBM primarily resemble internalized types such as phagocytosis. CONCLUSION: Mycobacterium tuberculosis-induced oligodendrocyte apoptosis promotes astrocyte-mediated CIC formation and phagocytosis, suggesting CIC as a novel pathophysiological mechanism in TBM.

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