MMPs and NETs are detrimental in CNS-tuberculosis with MMP inhibitor doxycycline improving murine CNS-tuberculosis survival (human)
Despite effective anti-tuberculous treatment (ATT), up to 40% of patients with central nervous system tuberculosis (CNS-TB) suffer permanent neurological deficits and death. The immunopathological mechanism of CNS-TB remains undefined, hindering the development of new CNS-TB therapies. We here report the spatial transcriptomics profiling of human CNS-TB and demyelination CNS tissues using laser capture microdissection RNA sequencing (LCM-RNA Seq). Human CNS-TB and demyelination samples exhibited distinct gene expression profiles based on cellular phenotypes. Genes involved in biological processes relates to cytokine responses, cell-substrate adhesion, extracellular matrix organization, inflammatory and immune responses are highly expressed in both inflammatory and granuloma tissues in contrast to demyelination and normal tissues. Down-regulated genes are associated with CNS-related processes such as synapse and cell junction organisation, myelination, neuron development and differentiation. Overall design: Clinical formalin-fixed paraffin-embedded (FFPE) samples were retrieved from human CNS-TB (n=6) and demyelination control (n=4). All tissue sections with 7 µm thickness each were stained with hematoxylin prior to LCM-RNA Seq. Target regions including granuloma, inflammatory region and adjacent normal regions were selected and microdissected for library construction. The libraries were sequenced and analysed.