Endogenous hepcidin plays an essential role in Mycobacterium tuberculosis Rv1876 antigen-induced antimicrobial activity in macrophages.

Tuberculosis (TB) is one of the most prevalent infectious diseases worldwide. However, few molecules related to bacterial killing within T cell-induced macrophages are known; therefore, elucidating host responses against bacterial components is critical for developing strategies to treat TB. This study investigated the anti-mycobacterial responses induced by Mycobacterium tuberculosis (Mtb) Rv1876 (bacterioferritin A). Rv1876 effectively activated macrophages; however, the protein itself did not elicit bacterial killing. When co-cultured with T cells (Rv1876-T cell), Mtb growth was substantially inhibited in Rv1876-activated macrophages. Rv1876-T cells enhanced endogenous hepcidin expression, an antimicrobial peptide, in Mtb-infected macrophages, which was co-localized adjacent to bacteria-containing phagosomes and directly interacted with them. Other major mycobacterial proteins and bacterioferritin B (Rv3841) did not induce hepcidin in Mtb-infected macrophages, irrespective of T cell involvement. These findings suggest that endogenous hepcidin induced by Rv1876-T cells may be a host bactericidal response and a promising target for host-directed therapies.