Mycobacterium tuberculosis induces differentiation imbalance of innate lymphoid cells via CD14 + monocytes/macrophages
10.3760/cma.j.cn311365-20240612-00168
- VernacularTitle:结核分枝杆菌通过CD14 ＋细胞诱导固有淋巴细胞亚群分化失衡的机制探讨
- Author:
Su ZHANG
1
;
Min OU
;
Xuefeng ZHOU
;
Yuping MO
;
Tingzhi CAO
;
Guoliang ZHANG
Author Information
1. 深圳市第三人民医院国家感染性疾病临床医学研究中心，深圳 518112
- Publication Type:Journal Article
- Keywords:
Mycobacterium tuberculosis;
Innate lymphoid cells;
Active pulmonary tuberculosis;
Mononuclear phagocyte
- From:
Chinese Journal of Infectious Diseases
2024;42(10):608-617
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the proportions of innate lymphoid cells (ILCs) subgroups during the process of Mycobacterium tuberculosis (MTB) infection, and to explore the molecular mechanism regulating the differentiation of ILCs during MTB infection. Methods:From March to October 2022, 31 patients with active pulmonary tuberculosis (ATB) and 17 patients who had recovered from pulmonary tuberculosis were enrolled from Shenzhen Third People′s Hospital. Additionally, 30 healthy controls were recruited from the physical examination department. Peripheral blood mononuclear cells (PBMCs) were extracted from all subjects, and the proportions of ILC, ILC1, ILC2 and ILC3 in lymphocytes of PBMCs from different populations were analyzed using flow cytometry. PBMCs from 18 healthy controls were induced in vitro with MTB H37Rv lysate or live Bacillus Calmette-Guérin (BCG) bacteria, and the differentiation of ILC subgroups was analyzed using flow cytometry. CD14 + cells from PBMCs of 29 healthy controls were isolated using magnetic bead sorting technology, and the cells were divided into three groups, including control group, CD14 - group, and CD14 + complement group. The CD14 + complement group was supplemented with CD14 + cells into CD14 - PBMCs through a Transwell chamber, and induced in vitro with H37Rv lysate. The differentiation of ILC subgroups was analyzed using flow cytometry. Statistical analyses were performed using Mann-Whitney U test, Kruskal-Wallis test, and Wilcoxon signed-rank test. Results:The proportions of ILCs in lymphocytes in healthy controls, ATB and recovered tuberculosis groups showed no statistically significant differences ( H=0.07, P=0.965). The proportion of ILC1 in lymphocytes in the peripheral blood of patients with ATB was lower than that in the healthy control group ( U=271.00), and the proportion of ILC2 was higher than that in the healthy control group ( U=299.00). The proportion of ILC1 in the peripheral blood of recovered tuberculosis patients was lower than that in the healthy control group ( U=123.00), and the proportion of ILC3 in the recovered tuberculosis group was higher than those in ATB and healthy control groups ( U=78.00 and 102.50, respectively). All differences were statistically significant (all P<0.05). Compared with the control group, the proportions of ILC ( W=-116.00 and -145.00, respectively) and ILC2 ( W=-149.00 and -155.00, respectively) in lymphocytes decreased after PBMCs induced by H37Rv lysate or BCG live bacteria (all P<0.05). The proportion of ILC1 showed no significant change after induction by H37Rv lysate ( W=-67.00, P=0.154), but decreased after induction by BCG ( W=-121.00, P=0.007) with statistical significance. There was no significant difference in the proportions of ILC1 in lymphocytes among control group, CD14 - group, and CD14 + complement group before and after induction by H37Rv lysate ( W=-159.00, 43.00 and -37.00, respectively, all P>0.05). The proportions of ILC2 in lymphocytes decreased after induction ( W=-435.00, -383.00 and -405.00, respectively) among the three groups, and the differences were all statistically significant (all P<0.001). The proportions of ILC3 in lymphocytes in the control group and CD14 + complement group decreased ( W=-250.00 and -262.00, respectively), and the differences were statistically significant (all P<0.05), while the proportion of ILC3 in lymphocytes in the CD14 - group did not change before and after induction, and the difference was not statistically significant ( W=-172.00, P=0.051). Conclusions:MTB infection induces an imbalance in the differentiation of ILCs subgroups, and the removal of CD14 + cells inhibits MTB-induced ILC3 differentiation without significantly affecting the differentiation of ILC1 and ILC2.
