Mycobacterium tuberculosis culture filtrate protein of 10 kDa inhibits B cell function (P3120)

Abstract

Abstract Culture filtrate protein 10 kD (CFP10) and early secreted antigenic target of 6 kD (ESAT-6), are required in pathogenesis of tuberculosis in part by manipulation of host immunity. We reported the immune modulatory effects of ESAT-6, and the effect of CFP10 in this regard remains unexplored. We now demonstrate that recombinant CFP10 binds to peripheral blood B cells and monocytes, but not to T-cells. Stimulation of B cells through the B cell receptor BCR plus TLR9 induced IL-6, IL-8 and IL-10 production, and CFP10 but not rAg85 markedly reduced IL-10 secretion and mRNA expression, without affecting IL-6 and IL-8. CFP10 did not affect LPS-stimulated cytokine production by monocytes. CFP10 reduced BCR plusTLR9 stimulated B cell proliferation and IgG secretion. Using B cells as antigen-presenting cells, we found that CFP10 inhibited expression of CD80 and CD86, but not that of CD69 and MHC-II expression, resulting in reduced M. tuberculosis-specific T cell IFN-γ production. The effects of CFP10 on B cells were not due to changes in B-cell TLR9 expression, viability or apoptosis. However, CFP10 inhibited BCR plus TLR9 stimulated nuclear translocation of NF-κB, activation of AP-1 transcription factors and expression of BLIMP1, the master regulator of B cell maturation and activation. We conclude that CFP10 inhibits B functions by blocking TLR9 and BCR signaling, suggesting potential cell specific immune regulatory functions for CFP10 during tuberculosis infection.