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Many subversive mechanisms promote the occurrence and development of chronic infectious diseases and cancer, among which the down-regulated expression of immune-activating receptors and the enhanced expression of immune-inhibitory receptors accelerate the occurrence and progression of the disease. Recently, the use of immune checkpoint inhibitors has shown remarkable efficacy in the treatment of tumors in multiple organs. However, the expression of immune checkpoint molecules on natural killer (NK) cells by Mycobacterium tuberculosis (Mtb) infection and its impact on NK cell effector functions have been poorly studied. In this review, we focus on what is currently known about the expression of various immune checkpoints in NK cells following Mtb infection and how it alters NK cell-mediated host cytotoxicity and cytokine secretion. Unraveling the function of NK cells after the infection of host cells by Mtb is crucial for a comprehensive understanding of the innate immune mechanism of NK cells involved in tuberculosis and the evaluation of the efficacy of immunotherapies using immune checkpoint inhibitors to treat tuberculosis. In view of some similarities in the immune characteristics of T cells and NK cells, we reviewed the molecular mechanism of the interaction between T cells and Mtb, which can help us to further understand and explore the specific interaction mechanism between NK cells and Mtb., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier GmbH.)

Human T cells and natural killer (NK) cells are major effector cells of innate immunity exerting potential immune surveillance against tuberculosis infection. CD226 is an activating receptor playing vital roles in the functions of T cells and NK cells during HIV infection and tumorigenesis. However, CD226 is a less-studied activating receptor during Mycobacterium tuberculosis (Mtb) infection. In this study, we used peripheral blood from tuberculosis patients and healthy donors to evaluate CD226 immunoregulation functions from two independent cohorts using Flow cytometry. Here, we found that a subset of T cells and NK cells that constitutively express CD226 exhibit a distinct phenotype in TB patients. In fact, the proportions of CD226 + and CD226 - cell subsets differ between healthy people and tuberculosis patients, and the expression of immune checkpoint molecules (TIGIT, NKG2A) and adhesion molecules (CD2, CD11a) in CD226 + and CD226 - subsets of T cells and NK cells exhibits special regulatory roles. Furthermore, CD226 + subsets produced more IFN-γ and CD107a than CD226 - subsets in tuberculosis patients. Our results imply that CD226 may be a potential predictor of disease progression and clinical efficacy in tuberculosis by mediating the cytotoxic capacity of T cells and NK cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Tuberculosis (TB) and type 2 diabetes mellitus (DM) are global health diseases with high morbidity and mortality. Few studies have focused on platelet indices in TB-DM coinfection patients. The objective of this work was to analyze the platelet indices in TB, DM and TB-DM patients to assess the predictive value of the platelet index for the risk of these diseases., Methods: In total, 246 patients admitted to our hospital were distributed into three groups (113 TB, 59 DM and 74 TB + DM). A total of 133 individuals were also recruited as healthy controls (HC). Platelet indices, namely, platelet count (PC), mean platelet volume (MPV), plateletcrit (PCT) and platelet distribution width (PDW), were compared among the four groups, and the relationship with inflammatory markers was explored by using statistical software., Results: Our study discovered that MPV and PCT were significantly downregulated in TB + DM patients (9.95 ± 1.25 fL, 0.20 ± 0.05%, P < 0.0001, P = 0.0121, separately) compared with DM individuals (10.92 ± 1.17 fL, 0.22 ± 0.04%). Moreover, the changes in MPV were significantly higher in TB + DM patients (9.95 ± 1.25 fL, P = 0.0041) than in TB patients (9.42 ± 1.01 fL). No differences were found in PLT and PDW among the four groups (P > 0.05). The sensitivity and specificity of MPV in the differential diagnosis of DM patients vs TB + DM patients were 64.9 and 66.1% (P < 0.0001), respectively, and the sensitivity and specificity of MPV between TB patients and TB + DM patients was 60.8 and 66.4%, respectively (P = 0.003). MPV improved the diagnosis sensitivity when it was combined with clinical parameters, such as fasting blood glucose in DM and Mycobacterium tuberculosis culture result in TB (76.3% vs 64.9, 72.6% vs 60.8%, P < 0.0001, P = 0.001, respectively). In addition, the sensitivity and specificity of PCT in the differential diagnosis of DM patients vs TB + DM patients were 69.5 and 59.4%, respectively (P = 0.008). PCT improved the diagnosis sensitivity when combined with fasting blood glucose in DM (72.9% vs 64.9%, P = 0.004). In addition, MPV was linked to CRP (C-reactive protein) and ESR (erythrocyte sedimentation rate) in the TB + DM patients (r = 0.3203, P = 0.0054, r = 0.2504, P = 0.0307) but PCT was not (r = 0.1905, r = 0.008675, P > 0.05, respectively)., Conclusions: Our research shows that MPV and PCT might be good clinical laboratory markers to distinguish TB + DM patients from TB or DM individuals, thus providing support for earlier clinical diagnosis, prevention, and therapy.

Background: There is a global focus on illness diagnosis in smear-negative and latent tuberculosis infectious populations (SN-TB and LTBI). CD27 has been suggested to play a direct role in active TB. Little is known about smear-negative individuals. Here, we tried to investigate whether it has a role in smear-negative populations. The expression of CD27 and MTB-specific CD27 in CD4+ T cells ("CD27−CD4+" and "CD27−IFN-γ+CD4+") was evaluated in MTB-unexposed controls (HC), TB contacts (TB-C) and SN-TB individuals by flow cytometry. The sensitivity, specificity and AUC (area under curve) of "CD27−IFN-γ+CD4+" cells to distinguish SN-TBs from HCs and TB-Cs were determined by receiver operating characteristic (ROC) curve analysis. The clinical index was selected from the clinical laboratory and evaluated for correlation with "CD27−IFN-γ+CD4+" cells by Spearman statistical analysis. Results: We observed that the percentages of "CD27−IFN-γ+CD4+" cells were significantly increased in the SN-TB group compared with the HC and TB-C groups (AUC was 0.88, sensitivity was 82.14%, specificity was 80.00%, and P < 0.0001). The percentage of "CD27−IFN-γ+CD4+" cells was negatively correlated with WBC (white blood cell count) (r = − 0.3019, P = 0.0182) and positively correlated with IgE (immunoglobulin E) (r = 0.2805, P = 0.0362). Furthermore, "CD27−IFN-γ+CD4+" cells were significantly decreased, especially in the > 50 years group, after clinical treatment. Conclusion: The present results demonstrated that the percentage of "CD27−IFN-γ+CD4+" cells might be a conceivable molecular indicator in the diagnosis of SN-TB and was influenced by its outcome of therapy. [ABSTRACT FROM AUTHOR]