Ex-vivo immunophenotyping and high dimensionality UMAP analysis of leucocyte subsets in tuberculous lymphadenitis

Tuberculosis (Edinb). 2021 Sep;130:102117. doi: 10.1016/j.tube.2021.102117. Epub 2021 Jul 31.

Abstract

Tuberculous lymphadenitis (TBL) is defined by reduced proinflammatory cytokines and elevated CD4+, CD8+ T cells and decreased CD8+ cytotoxic markers. However, ex-vivo phenotyping of diverse leucocytes in TBL has not been done. We show activated and atypical B cells, myeloid dendritic cells (mDCs), classical, non-classical and intermediate monocytes, T regulatory (T regs) cells, CD4+ T cell effector memory RA (TEMRA), CD4+ effector and CD8+ central memory phenotypes were significantly increased in TBL compared to LTB individuals. In contrast, classical memory and plasma B cells, plasmacytoid DCs (pDCs), CD8+ TEMRA, CD4+ naïve and central memory cells were significantly decreased in TBL compared to LTB individuals. Some of the leucocyte frequencies (atypical memory B cells, pDCs, myeloid-derived suppressor cells, CD4+ effector and CD8+ central memory was increased; activated memory and plasma B cell, mDCs, classical, non-classical, intermediate monocytes, T regs, CD4+ TEMRA, CD4+, CD8+ naïve and effector memory cells and CD8+ central memory cells were decreased) were significantly modulated after anti-TB treatment among TBL individuals. UMAP analysis show that leucocyte subsets or islands expressing specific markers were significantly different in TBL baseline and post-treatment individuals. Overall, we suggest altered frequencies of diverse leucocytes influences the disease pathology and protective immunity in TBL individuals.

Keywords: B cells; Dendritic cells; Flow cytometry; Memory T cells; Monocytes; T regs; UMAP analysis.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • B-Lymphocytes / immunology*
  • Dendritic Cells / immunology
  • Female
  • Humans
  • Immunophenotyping
  • Male
  • Middle Aged
  • Monocytes / immunology
  • T-Lymphocyte Subsets / immunology*
  • Tuberculosis, Lymph Node / immunology*
  • Young Adult