Proteomic analysis reveals critical molecular mechanisms involved in the macrophage anti-spinal tuberculosis process

Tuberculosis infection activates the autoimmune system. However, the role of host-pathogen interactions involved in Mycobacterium tuberculosis infection is unclear. In this study, we analyzed 6 spinal tuberculosis tissues and 6 herniated disc tissues by using liquid chromatography-tandem mass spectrometry coupled with tandem mass spectrometry, and immunohistochemical staining was performed for validating the results. We identified 42 differential immune-related proteins and 3 hub genes that are primarily localised in the tertiary granule and involved in biological processes such as cellular response to the presence of cadmium ions, regulation of ion transmembrane transport, transmembrane transport, and inflammatory responses. Genes encoding cytochrome B-245 beta chain (CYBB), matrix metallopeptidase 9 (MMP9), and C-X-C motif chemokine ligand 10 (CXCL10) were identified as the hub genes that exhibited anti-tuberculosis activity and were responsible for macrophage resistance against M. tuberculosis. In conclusion, CYBB, MMP9, and CXCL10 resist M. tuberculosis infection through chemotaxis and macrophage activation. Our results indicate that CYBB, MMP9, and CXCL10 could be considered as molecular targets for spinal tuberculosis treatment, which may significantly improve patients' quality of life and prognosis.