Mycobacterium tuberculosis Rv3641c inhibits macrophage type Ⅰ interferon responses and promotes intracellular survival in macrophages
10.3969/j.issn.1002-2694.2025.00.062
- VernacularTitle:结核分枝杆菌Rv3641c抑制巨噬细胞Ⅰ型干扰素应答并促进胞内存活的研究
- Author:
Wen JIN
1
;
Min GENG
;
Su-jie HU
;
Xin-yang ZHANG
;
Wen-qin LI
;
Cheng-kun ZHENG
;
Xin-an JIAO
;
Xiang CHEN
;
Zheng-zhong XU
Author Information
1. 扬州大学/江苏省人兽共患病学重点实验室,江苏省动物重要疫病与人兽共患病防控协同创新中心,扬州 225009
- Publication Type:Journal Article
- Keywords:
Mycobacterium tuberculosis;
type I interferon;
immune escape;
intracellular survival;
Rv3641c
- From:
Chinese Journal of Zoonoses
2025;41(4):385-391
- CountryChina
- Language:Chinese
-
Abstract:
This study was aimed at investigating the immunoregulatory function of Mycobacterium tuberculosis Rv3641c gene in modulating host type Ⅰ interferon responses.The shuttle plasmid pMV261 was used to construct Rv3641c overexpression recombinant Mycobacterium smegmatis,and the biological characteristics of the recombinant bacteria were analyzed to explore the effect of Rv3641c on the growth curve,colony morphology and stress resistance of Mycobacterium.Subsequently,RAW264.7 cells were infected with Rv3641c overexpressing Mycobacterium smegmatis,and the transcriptional expression of genes related to the inhibition of type I inter-feron pathway was determined by RT-PCR.The expression level of IFN-βprotein was determined by ELISA,and the intracellular sur-vival level was determined.As a result,the recombinant rMS::pMV261-Rv3641c was successfully constructed.The results of biologi-cal characteristics analysis showed that Rv3641c did not affect the growth of mycobacteria,but significantly changed the colony mor-phology of mycobacteria and improved its resistance to H2O2.The results of recombinant bacteria infection experiments showed that Rv3641c significantly down-regulated the transcription levels of IFN-α,IFN-βand downstream ISGs genes CXCL10,IFIT2 and IL-1β in host cells,and Rv3641c significantly down-regulated the transcription levels of IFN-α,IFN-βand downstream ISGs genes CXCL10,IFIT2 and IL-1βin host cells.The results of intracellular colonization experiments showed that the intracellular mycobacte-ria in the overexpression recombinant bacteria infection group were significantly higher than those in the empty vector group,indicat-ing that Rv3641c could promote the intracellular surviv al of mycobacteria.In summary,the Rv3641c gene of M.tuberculosis can inhibit the host type I interferon response and promote the intracellular survival of M.tuberculosis,which provides a new idea for further explor-ing the immune escape function of M.tuberculosis and the discovery of new targets for anti-tuberculosis drugs.
