HDAC6 plays an immuneprotective role against Chlamydia muridarum respiratory infection by inhibiting specific CD4 + Th2 response
10.3760/cma.j.cn112309-20240613-00213
- VernacularTitle:HDAC6通过抑制衣原体特异性CD4 ＋Th2应答发挥抗衣原体呼吸道感染免疫保护作用
- Author:
Lu TAN
1
;
Jinxi YU
1
;
Yuqing TUO
1
;
Shuaini YANG
1
;
Ruoyuan SUN
1
;
Jiajia ZENG
1
;
Hong ZHANG
1
;
Hong BAI
1
Author Information
1. 天津医科大学基础医学院免疫学系，国家教育部免疫微环境与疾病重点实验室，天津市细胞和分子免疫学重点实验室，天津 300070
- Publication Type:Journal Article
- Keywords:
Chlamydia trachomatis;
HDAC6;
Adaptive immune response;
CD4 + T cell;
Th2
- From:
Chinese Journal of Microbiology and Immunology
2025;45(5):366-372
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the mechanism by which histone deacetylase 6 (HDAC6) exerts immune protective effects in Chlamydia trachomatis respiratory tract infection. Methods:Wild-type (WT) C57BL/6 mice and HDAC6 gene knockout (HDAC6 -/-) mice were used to establish mouse models of Chlamydia muridarum ( Cm) respiratory infection by nasal inhalation of Cm. qPCR and Western blot were used to detect the relative expression of HDAC6 in lung tissues of WT mice after Cm infection. Intracellular factor staining was used to detect the percentages and absolute numbers of CD4 + T cell subsets (Th1, Th17 and Th2 cells)in mouse lung tissues after infection. The levels of IL-4 in spleen cell culture supernatants were measured by ELISA. One-way or two-way analysis of variance (ANOVA) was used for statistical analysis. Results:Cm respiratory tract infection significantly promoted the expression of HDAC6 at both mRNA and protein levels in lung tissues of WT mice ( P<0.001). HDAC6 -/- mice lost more weight than WT mice and took longer to recover to the normal level. Chlamydia load ( P<0.001 and P<0.05) and pathological damage ( P<0.05 and P<0.000 1) in lung tissues were more serious in HDAC6 -/- mice than in WT mice at 7 and 14 d after infection. Neither the percentage nor the absolute number of Th1 (CD4 + IFN-γ + T) and Th17 (CD4 + IL-17 + T) cells showed significant differences between WT and HDAC6 -/- mice, while the percentage and absolute number of Th2 (CD4 + IL-4 + T) cells increased in HDAC6 -/- mice ( P<0.05 and P<0.01). Moreover, in HDAC6 -/- mice, the expression of IL-4 mRNA increased ( P<0.000 1) and the level of IL-4 in the splenic cell culture supernatants increased ( P<0.01). Conclusions:HDAC6 plays an immune protective role in Cm infection. It can reduce the susceptibility of host to Cm respiratory tract infection and alleviates the pathological damage in lung tissues by inhibiting the immune response of Th2 cells.
