DosR antigen Rv1737c induces activation of macrophages dependent on the TLR2 pathway

Latent Mycobacterium tuberculosis (Mtb) infection (LTBI) is the main clinical manifestation after Mtb exposure. During the latent phase, Mtb retards the attempts of eradication by the host immune system. The dormancy survival regulator (DosR) is held as essential for Mtb persistence. Rv1737c is predominantly expressed by the Mtb in latent infection. However, the role of Rv1737c in the immune evasion is still largely unknown. In this study, we have characterized the Rv1737c functions in the recruitment and activation of macrophages, which play a cardinal role in the innate and adaptive immunity. For the first time, we have revealed that Rv1737c induced the tolerogenic phenotype of macrophages by upregulating the expression of indoleamine 2,3-dioxygenase 1 (IDO1). Rv1737c-activated macrophages upregulated interleukin (IL)-4, IL-10, and Foxp3 T cells proliferation in vitro. Furthermore, the interaction of Rv1737c with macrophages was found to depend on the Toll-like receptor 2 (TLR2) pathway. It augmented nuclear factor κB (NF-κB) phosphorylation and co-stimulatory molecule expression. Thus, this study provides a crucial insight into a strategy adopted by Mtb to survive in the host by inducing tolerogenic macrophage expansion.