Secreted Rv1768 From RD14 of Mycobacterium tuberculosis Activates Macrophages and Induces a Strong IFN- γ-Releasing of CD4+ T Cells

In this study, we further determined that Rv1768 was highly conserved among virulent M.tb strains and mainly distributed as a secreted protein. Exposure to recombinant purified Rv1768 (rRv1768) induced apoptosis of bone marrow derived macrophages (BMDMs) but showed no dose-dependent manner. Regarding macrophage activation, significant higher levels of iNOS and pro-inflammatory cytokines (like IL-6 and TNF-α) were detected in rRv1768-challenged BMDMs, whereas arginase 1 (Arg1) expression was markedly decreased. Meanwhile, MHC-II expression and antigen presentation activity of BMDMs were also enhanced by rRv1768 stimulation, leading to significantly increased IFN-γ expression of CD4+ T cells isolated from H37Rv-infected mice. It is worthy to note that Rv1768-induced IFN-γ production of peripheral blood mononuclear cells (PBMCs) and Rv1768-specific immunoglobulins was specifically observed in H37Rv-infected mice, but not BCG-infected or normal mice. Analysis of clinical blood samples further revealed that Rv1768 had a higher sensitivity and specificity (91.38 and 96.83%) for tuberculosis diagnosis than the results obtained from clinical CFP10 and ESAT6 peptides (CE)-based enzyme-linked immunospot (ELISPOT) assay. The area under ROC curve of Rv1768 was 0.9618 (95% CI: 0.919–1.000) when cutoff value set as 7 spots. In addition, Rv1768-specific IgG and IgM also exhibited moderate diagnostic performance for tuberculosis compared with CE specific antibodies. Our data suggest tha...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research