Statistical and network analyses reveal mechanisms for the enhancement of macrophage immunity by manganese in Mycobacterium tuberculosis infection

Tuberculosis is a significant infectious disease that poses a serious risk to human health. Our previous research has indicated that manganese ions reduce the bacterial load of Mycobacterium tuberculosis in macrophages, the exact immune defense mechanism remains unknown. Several critical proteins and pathways involved host's immune response during this process are still unidentified. Our research aims to identify these proteins pathways and provide a rationale for the use of manganese ions in the adjuvant treatment of tuberculosis. downloaded GSE211666 data from the GEO database and selected the RM (Post-infection manganese treatment group) and Ra (single-infection group) groups for comparison and analysis to identify differential genes. These differential genes were then enriched and analyzed using STRING, Cytoscape, and NDEx tools identify the two most relevant pathways of the "Host Response Signature Network." After conducting an in-depth analysis of these two pathways, we found that manganese ions mainly mediate (1) the interferon-gamma and its receptor IFNGR and the downstream JAK-STAT pathway and (2) the NF kappa B pathway to enhance phage response to interferon, autophagy, polarization, and cytokine release. Using qPCR experiments, verified the increased expression of CXCL10, MHCII, IFN gamma, CSF2, and IL12, all of which are cytokines that key role in resistance to Mycobacterium tuberculosis infection, suggesting that macrophages enter a state inflammatory and activation after the addition of manganese ions, which enhances their immunosuppressive effect against Mycobacterium tuberculosis. We conclude that our study provides evidence of manganese ability to treat tuberculosis adjuvantly.