Intracerebral Mycobacterium bovis bacilli Calmette–Guerin infection-induced immune responses in the CNS

To study whether cerebral mycobacterial infection induces granuloma and protective immunity similar to systemic infection, we intracerebrally infected mice with Mycobacterium bovis bacilli Calmette–Guerin. Granuloma and IFN-γ⁺CD4⁺ T cell responses are induced in the central nervous system (CNS) similar to periphery, but the presence of IFN-γIL-17 double-positive CD4⁺ T cells is unique to the CNS. The major CNS source of TNF-α is microglia, with modest production by CD4⁺ T cells and macrophage. Protective immunity is accompanied by accumulation of Foxp3⁺CD4⁺ T cells and PD-L2⁺ dendritic cells, suggesting that both inflammatory and anti-inflammatory responses develop in the CNS following mycobacterial infection.