Manganese as a Cofactor in the Immunity of Mycobacterium tuberculosis Infection.

Mycobacterium tuberculosis (Mtb), a highly infectious intracellular pathogen, is the primary causative agent of tuberculosis (TB), which ranks as the leading cause of death from individual infectious agents. In this context, we developed a model using macrophages infected with M. smegmatis mc2155 and Mtb H37Ra to elucidate the role of Mnin host defense against tuberculosis infection. Treatment with a combination of anti-tuberculosis drugs and Mnfor 36 h markedly reduced the survival of intracellular bacteria, and the addition of Mnsignificantly enhanced the secretion of TNF-α and IL-1β. In mice infected with Mtb H37Ra, treatment with Mn(2 mg/kg) and the combination of Isoniazid and Mnsignificantly increased serum TNF-α levels, with the combination treatment showing a more pronounced effect. Histopathological analysis indicated a relatively diminished immune response in the spleen in the drug and Mntreatment groups, while the immune response in the lungs was comparable across all groups. Mncan synergistically enhance the efficacy of anti-tuberculosis drugs by activating cellular secretion of immune factors and inhibiting the growth of Mtb. The findings of this study provide a rationale for the potential use of Mnas an activator of cellular immunity against Mtb infection.