Single-cell transcriptome reveals highly complement activated microglia cells in association with pediatric tuberculous meningitis

• DOI: 10.3389/fimmu.2024.1387808
• Publication Date: 2024-04-30T05:08:54Z
• Authors: Siwei Mo; Chenyan Shi; Yi Cai; Maozhu Xu; Hongmei Xu; Yuzhong Xu; Kehong Zhang; Yue Zhang; Jiao Liu; Siyi Che; Xiangyu Liu; Chaonan Xing; Xiaoru Long; Xinchun Chen; Enmei Liu
• Keywords: Monocyte

Background Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB) causing high mortality and disability. TBM arises due to immune dysregulation, but the underlying mechanisms are unclear. Methods We performed single-cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) cerebrospinal fluid (CSF) isolated from children (n=6) with using 10 xGenomics platform. used unsupervised clustering cluster visualization based gene expression profiles, validated protein cytokines by ELISA analysis. Results revealed for first time 33 monocyte populations across CSF PBMCs TBM. Within these populations, we saw that CD4_C04 Th17 Th1 phenotypes Macro_C01 microglia phenotype, were enriched in CSF. Lineage tracking analysis myeloid cell as well subsets CD4 CD8 T-cell distinct effector functions. Importantly, discovered complement-activated microglial associated neuroinflammatory response leads persistent meningitis. Consistently, an increase complement (C1Q), inflammatory markers (CRP) factor (TNF-α IL-6) not blood. Finally, inferred recruit through CXCL16/CXCR6. Discussion proposed subset activates interacts amplify signals, which could potentially contribute augment resulting hyperinflammation elicited Mtb -infected tissues.