The DosR antigen Rv1737c from Mycobacterium tuberculosis confers inflammation regulation in tuberculosis infection

: 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 (rRv1737c) exhibited higher levels of antigen-specific antibodies (IgG, IgM and IgA) than sham-treated mice. Following Bacilli Calmette-Guerin (BCG) challenge, rRv1737c adjuvanted with cholera toxin subunit B (CTB) induced diffuse lung inflammation and fibrosis compared to the control mice. The inflammatory pathogenesis due to rRv1737c 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 rRv1737c-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 rRv1737c pretreatment compared to that in the sham mice. Accordingly, lung cells from rRv1737c-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 rRv1737c promoted inflammation. Overall, our findings provide direct evidence of the pro-inflammatory function of rRv1737c 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.