Single-cell transcriptome sequencing reveals altered peripheral blood immune cells in patients with severe tuberculosis.

Tuberculosis is a serious global health burden, resulting in millions of deaths each year. Several circulating cell subsets in the peripheral blood are known to modulate the host immune response to Mycobacterium tuberculosis (Mtb) infection in different ways. However, the characteristics and functions of these subsets to varying stages of tuberculosis infection have not been well elucidated. Peripheral blood immune cells (PBICs) were isolated from healthy donors (HD group), individuals with mild tuberculosis (MI group), and individuals with severe tuberculosis (SE group). CD4+ naive T cells and CD8+ T cells were decreased in the SE and MI groups, while CD14+ monocytes were increased in the SE group. Further analysis revealed increased activated CD4+ T cells, transitional CD8+ T cells, memory-like NK cells, and IGHG3^highTTN^highFCRL5^high B cells were increased in all patients with tuberculosis (SE and MI group). In contrast, Th17 cells, cytotoxic NK cells, and cytotoxic CD4+ T cells were decreased. Moreover, the increase of CD14+CD16+ monocytes correlated with severe tuberculosis, and the GBP5^highRSAD2^high neutrophils were unique to patients with severe tuberculosis. Cellular communication analysis revealed that CD8+ T cells exhibited the highest incoming interaction strength in the SE group. The increased CD8+ T cell incoming interactions are associated with the MHC-I and LCK pathways, with HLA-(A-E)-CD8A, HLA-(A-E)-CD8B, and LCK-(CD8A+CD8B) being ligand-receptor pairs. Patients with tuberculosis, especially severe tuberculosis, have profound changes in peripheral blood immune cell profiles. CD8+ T cells showed the highest incoming interaction strength in patients with severe tuberculosis, with the main signals being MHC-I and LCK pathways.