Latency-associated protein Rv2660c of Mycobacterium tuberculosis augments expression of proinflammatory cytokines in human macrophages by interacting with TLR2

Abstract

Background: One-third of the world's human population is latently infected with Mycobacterium tuberculosis (Mtb), and individuals with latent infection have a 10% risk of developing active tuberculosis (TB) disease in their lifetime. Rv2660c (encoding a hypothetical protein) is closely correlated with dormancy of Mtb. Studies have found that Rv2660c was preferentially expressed during latent infection for adaptation to lack of nutrition and hypoxia; however, the precise function is unknown. Identification and characterization of Rv2660c is crucial to understand host–pathogen interactions and to develop drug targets and vaccine candidates. Methods: This study investigated the functional roles and the related signaling mechanism of Rv2660c interacting with human macrophages. Results: The results showed that either rBCG-Rv2660c strain (expressing Rv2660c protein) or recombinant purified Rv660c protein was able to stimulate peripheral blood mononuclear cells (PBMCs) and phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells to secrete the important cytokines interleukin (IL)-1β, IL-8, tumor necrosis factor (TNF)-α, and IL-12p70, which are essential for granuloma formation and maintenance. Meanwhile, Rv2660c recognized Toll-like receptor 2 (TLR2) to activate macrophages. Conclusion: The results suggested that Rv2660c was able to stimulate human macrophages to provoke the secretion of proinflammatory cytokines by interacting with TLR2 signaling, and the proinflammatory responses elicited by Rv2660c might be an important way to maintain latency of Mtb.

Keywords::

• Latency-associated protein
• Rv2660c
• macrophage
• proinflamatory cytokine
• Toll-like receptor 2
• TLR2

Declaration of interest: This study was supported by the Scientific Research Fund of Kunming University of Science and Technology (no. KKSY201360112).