Role of invariant nature killer T cell in dysbiosis of gut microbiota among Mycobacterium tuberculosis infected patients

Abstract

Abstract Background In Mycobacterium tuberculosis (MTB)-infected patients, the dysbiosis in gut microbiota was associated with systemic proinflammation. The invariant nature killer T (iNKT) cell was suggested the T-cell involved in immune modulation activated by metabolites or structural molecules of microbial in gut lumen. Herein we investigated how the gut microbiota influence on the systemic immunity by study the iNKT cells in peripheral blood in human. Method Patients with active TB, latent TB infection (LTBI), and healthy controls (HC) were enrolled. Interleukin (IL)-10, IL-4, IL-6, and IL-1B levels, the CD3+, CD4+, CD8+ cells, iNKT (CD3+6B11+) cells counts in blood, proliferation index (PI) of iNKT cells by α-galactosylceramide (α-GalCer) stimulation in vitro, and the interferon-gamma (IFN-γ) concentration by IFN-r-releasing-assay (IGRA) were measured. Results In active TB, both the cell counts and PI of iNKT were decreased. In LTBI, the PI of iNKT cells and the stimulated IFN-γ by MTB-Antigen divided to the iNKT cell counts (IFN-TBAg/iNKT) were positively associated with the relative abundance of Firmicutes. In active TB, a higher iNKT cell counts were also associated with higher relative abundance of Firmicutes. After adjusted by iNTK cell counts, the proinflammatory cytokines IL-10, IL-1B, and IL-6 were positively associated with the relative abundance of Bacteroidaceae in the gut microbiota. Conclusion In LTBI, Firmicutes in the gut microbiota determined the activities of iNKT cell and the IFN-TBAg level in peripheral blood. In active TB, the iNKT cell was related to the pro-inflammation and the relative abundances of Bacteroidaceae in gut microbiota.