Expression and clinical significance of peripheral blood NK cell surface co-signaling molecules in active pulmonary tuberculosis patients.

OBJECTIVE: The aim of this study is to elucidate the expression of co-signaling molecules on NK cells following tuberculosis (TB) infection.

METHODS: We analyzed peripheral blood mononuclear cells (PBMCs) from healthy controls (HC), individuals with latent tuberculosis infection (LTBI), and patients with active pulmonary tuberculosis (PTB). Using full-spectrum multi-parametric flow cytometry, we assessed the distribution of co-signaling molecules on the surface of NK cells, both without and with stimulation with tuberculosis-specific antigens ESAT6 and CFP10. 7 inhibitory receptors, and 6 co-stimulatory receptors were analyzed.

RESULTS: The proportion of NK cells was significantly higher in the LTBI individuals compared to HC (P = 0.0199) and TB patients (P = 0.0027). In the absence of tuberculosis-specific antigen stimulation, the expression of TIGIT and TIM-3 were higher in the LTBI group compared to the TB group (P = 0.0128, P = 0.0340). The expression of CD160 in the TB group was significantly lower than in the HC and LTBI individuals (P = 0.0042, P = 0.0124). Upon stimulation with tuberculosis-specific antigens, the expression of OX40 was markedly elevated in LTBI and TB compared to HC (LTBI vs. HC, P = 0.0031; TB vs. HC, P = 0.0493), and the expression of CRTAM in the TB group was obviously higher than in HC (P = 0.0192).

CONCLUSION: Expression of co-signaling molecules on NK cells, including TIGIT, TIM-3, CD160, OX40, and CRTAM, was altered following TB infection. Our findings may provide potential targets for host-directed immunotherapy and novel vaccine development for TB.

CLINICAL TRIAL: Not applicable.