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The DosR antigen Rv1737c from Mycobacterium tuberculosis confers inflammation regulation in tuberculosis infection
Author(s) -
Gao Xiaoling,
Wu Cong,
Wang Xiaoxia,
Xu Hui,
Wu Yu,
Li Yonghong,
Jia Yanjuan,
Wei Chaojun,
He Wenhua,
Wang Yongxiang,
Zhang Benzhong
Publication year - 2019
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12729
Subject(s) - immunology , antigen , tuberculosis , spleen , immune system , inflammation , mycobacterium tuberculosis , cytokine , medicine , antibody , pathogenesis , macrophage , biology , pathology , in vitro , biochemistry
There is an urgent need to identify the potential risk factors for activating latent Mycobacterium tuberculosis infection. In this study, we evaluated the immune function of Rv1737c, which is a latency‐associated antigen of dormancy survival regulator (DosR) of M. tuberculosis in a mouse model. Our data showed that mice pretreated with recombinant Rv1737c ( rR v1737c) exhibited higher levels of antigen‐specific antibodies (IgG, IgM and IgA) than sham‐treated mice. Following Bacilli Calmette‐Guerin ( BCG ) challenge, rR v1737c adjuvanted with cholera toxin subunit B ( CTB ) induced diffuse lung inflammation and fibrosis compared to the control mice. The inflammatory pathogenesis due to rR v1737c pre‐exposure was associated with a switch in the macrophage phenotype from M1 to activated M2 and was characterized by IL ‐10 production. Intracellular cytokine analysis further showed that the rR v1737c‐pretreated mice exhibited an increased frequency of Th2 cells in the lungs, lymph nodes and spleen after BCG challenge. Furthermore, IFN ‐γ expression increased in the lungs after rR v1737c pretreatment compared to that in the sham mice. Accordingly, lung cells from rR v1737c‐immunized mice stimulated with killed BCG produced higher levels of multiple cytokines, such as IFN ‐γ, IL ‐10 and IL ‐6. The results confirmed that the pathological features of rR v1737c promoted inflammation. Overall, our findings provide direct evidence of the pro‐inflammatory function of rR v1737c in a murine model of BCG infection, indicating that Rv1737c is a pathogenic antigen of M. tuberculosis and may be key to the recurrence of latent infection.