National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
National Institute for Research in Tuberculosis (NIRT), Chennai, India.
J Immunol Res. 2022 Feb 21;2022:2422790. doi: 10.1155/2022/2422790. eCollection 2022.
Natural killer (NK) and invariant NKT (iNKT) cells are unique innate lymphocytes that coordinate diverse immune responses and display antimycobacterial potential. However, the role of NK and iNKT cells expressing cytokines, cytotoxic, and immune markers in latent tuberculosis (LTB), diabetes mellitus (DM), or preDM (PDM) and nonDM (NDM) comorbidities is not known. Thus, we have studied the unstimulated (UNS), (Mtb [PPD, WCL]), and mitogen (P/I)-stimulated NK and iNKT cells expressing Type 1 (IFN, TNF, and IL-2), Type 17 (IL-17A, IL-17F, and IL-22) cytokines, cytotoxic (perforin, granzyme B, and granulysin) and immune (GMCSF, PD-1, and CD69) markers in LTB comorbidities by dimensionality reduction and flow cytometry. Our results suggest that LTB DM and PDM individuals express diverse NK and iNKT cell immune clusters compared to LTB NDM individuals. In UNS condition, frequencies of NK and iNKT cells expressing markers are not significantly different. After Mtb antigen stimulation, NK cell expressing [Type 1 (IFN, TNF, and IL-2), GMCSF in PPD and IFN in WCL), Type 17 [(IL-17A), PD-1 in PPD), (IL-17A, IL-17F, and IL-22), PD-1 in WCL], and cytotoxic (perforin, granzyme B in PPD, and WCL)] marker frequencies were significantly reduced in LTB DM and/or PDM individuals compared to LTB NDM individuals. Similarly, iNKT cells expressing [Type 1 (IFN, IL-2), GMCSF in PPD), TNF, GMCSF in WCL), Type 17 (IL-17A), PD-1 in PPD, IL-17F in WCL) cytokines were increased and cytotoxic or immune (perforin, granzyme B, granulysin), CD69 in PPD, perforin and CD69 in WCL] marker frequencies were significantly diminished in LTB DM and/or PDM compared to LTB NDM individuals. Finally, NK and iNKT cell frequencies did not exhibit significant differences upon positive control antigen stimulation between the study population. Therefore, altered NK cell and iNKT cells expressing cytokines, cytotoxic, and immune markers are characteristic features in LTB PDM/DM comorbidities.
自然杀伤 (NK) 和不变自然杀伤 T (iNKT) 细胞是独特的先天淋巴细胞，它们协调多种免疫反应并显示出抗分枝杆菌的潜力。然而，在潜伏性结核 (LTB)、糖尿病 (DM) 或预糖尿病 (PDM) 和非糖尿病 (NDM) 合并症中，表达细胞因子、细胞毒性和免疫标志物的 NK 和 iNKT 细胞的作用尚不清楚。因此，我们通过降维和流式细胞术研究了未刺激 (UNS)、(Mtb [PPD、WCL]) 和有丝分裂原 (P/I) 刺激的表达 1 型 (IFN、TNF 和 IL-2)、17 型 (IL-17A、IL-17F 和 IL-22) 细胞因子、细胞毒性 (穿孔素、颗粒酶 B 和颗粒溶素) 和免疫 (GMCSF、PD-1 和 CD69) 标志物的 NK 和 iNKT 细胞。我们的结果表明，与 LTB NDM 个体相比，LTB DM 和 PDM 个体表达不同的 NK 和 iNKT 细胞免疫群。在 UNS 条件下，表达标志物的 NK 和 iNKT 细胞的频率没有显著差异。在 Mtb 抗原刺激后，表达 [1 型 (IFN、TNF 和 IL-2)、GMCSF 在 PPD 和 IFN 在 WCL)、17 型 [(IL-17A)、PD-1 在 PPD)、(IL-17A、IL-17F 和 IL-22)、PD-1 在 WCL)] 和细胞毒性 (穿孔素、颗粒酶 B 在 PPD 和 WCL)] 标志物频率的 NK 细胞显著降低在 LTB DM 和/或 PDM 个体与 LTB NDM 个体相比。同样，表达 [1 型 (IFN、IL-2)、GMCSF 在 PPD)、TNF、GMCSF 在 WCL)、17 型 (IL-17A)、PD-1 在 PPD、IL-17F 在 WCL)] 和细胞毒性 (穿孔素、颗粒酶 B、颗粒溶素)、CD69 在 PPD、穿孔素和 CD69 在 WCL) 标志物频率的 iNKT 细胞增加，并且在 LTB DM 和/或 PDM 个体与 LTB NDM 个体相比显著降低。最后，NK 和 iNKT 细胞频率在阳性对照抗原刺激后在研究人群之间没有表现出显著差异。因此，表达细胞因子、细胞毒性和免疫标志物的 NK 细胞和 iNKT 细胞的改变是 LTB PDM/DM 合并症的特征。
