Tuberculosis remains a chronic infectious disease that poses a serious threat to human health and the work to control tuberculosis remains very challenging. Host-directed therapy (HDT) may represent a novel anti-tuberculosis treatment strategy worthy of attention and further exploration. The purpose of this study was to investigate the regulatory role of GPR84, a member of the G protein-coupled receptor (GPCR) family in Mycobacterium bovis Bacillus Calmette-Guérin(BCG) infection. In this study, wild-type C57BL/6 mice (WT Group) and Gpr84 gene-deficient mice (Gpr84－/－ group) were used as controls to establish a high-dose BCG infection mouse model. The differences in the amount of bacteria in lungs, spleen, liver, kidney and other organs and the severity of lung pathological damage between Gpr84 gene-deficient mice and wild-type mice were evaluated by CFU assay, lung tissue HE staining and acid-fast staining. The changes of body weight and general condition of mice in the two groups were observed. The results showed that Gpr84 gene-deficient mice infected with BCG exhibited a significant decrease in body weight compared to uninfected mice. The colony-forming unit (CFU) results and acid-fast staining showed that bacterial load in lung tissues of Gpr84－/－ group was higher than that of WT group, and the differences of bacterial load in spleen and liver were consistent with those in lung. HE staining revealed that the normal alveolar structure of lung tissues of Gpr84－/－ group was significantly more damaged than that of WT group after BCG infection, with a higher number of lesions observed. Flow cytometric analysis of lung cells of mice indicated that in the absence of infection, the knockout of Gpr84 had no significant effect on the number of resident alveolar macrophages (AMs) and interstitial macrophages (IMs) in the lungs. And in acute infection, the proportion of AMs in the lungs of mice in Gpr84 －/－group was significantly higher than in WT group, while the proportion of IMs was significantly lower than in WT group, the proportion of mononuclear phagocytes (MNPs) Ly6Chi subpopulation was increased. The number of Ly6Clo subpopulation was decreased, and neutrophils (Neuts) infiltration was increased. The results revealed that the aggravated bacterial load and pathological damage after Gpr84 knockout may be related to the reduction of the relative ratio of IMs/AMs and the increase of the Ly6Chi MNPs subgroup, affecting its transformation to the Ly6Clo subgroup and increasing the infiltration of Neuts. Therefore, Gpr84 may serve as a potential target for host-directed therapy of tuberculosis through its role in immune regulation.
MA Jia-Ye
,
LV Shui-Hua
. Study on the regulation of Gpr84 gene in mice infected with mycobacterium bovis Bacillus Calmette-Guérin[J]. Journal of Microbes and Infections, 2024
, 19(5)
: 280
-291
.
DOI: 10.3969/j.issn.1673-6184.2024.05.003
