IL-36γ enhanced bactericidal effects of macrophages to Mycobacterium tuberculosis via the IFN-γ/HIF-1ɑ/glycolysis...

IL-36γ coordinates macrophage activation and is essential for defense against Mycobacterium tuberculosis (Mtb), but the mechanisms remains poorly understood. Aerobic glycolysis plays a critical role in macrophages intrinsic control of Mtb infection. This study aimed to investigate the potential effects of IL-36γ on macrophages energy metabolism transformation from mitochondrial oxidative phosphorylation to aerobic glycolysis in response to Mtb infection.

The expression of IL-36γ in lung tissues, PBMCs and serum was analyzed using Immunohistochemistry, ELISA and RT-qPCR, while the role and mechanism of IL-36γ on macrophages energy metabolism transformation duing Mtb infection were investigated by RT-qPCR, ELISA, Western blot and colony-forming unit assay.

We demonstrated IL-36γ enhanced the aerobic glycolysis, and downregulated the mitochondrial oxidative phosphorylation in Mtb infected macrophages. Furthermore, IL-36γ upregulated the expression of HIF-1α and IFN-γ in macrophages through the NF-κB/ERK/JNK signaling pathway, especially in macrophages infected with Mtb, where it induced the expression of large amounts of HIF-1α and IFN-γ. Moreover, IL-36γ promoted aerobic glycolysis through inducing the expression of HIF-1α in macrophages during Mtb infection. Meanwhile, HIF-1α was required for IL-36γ-mediated control of Mtb infection. Interestingly, the expression of IL-36γ was increased in lung tissues, PBMCs and serum from patients with active pulmonary tuberculosis and correlated with monocytes/macrophages immune response and IFN-γ levels, displayed an appreciable diagnostic value.

IL-36γ enhanced bactericidal effects of macrophages to Mycobacterium tuberculosis via the IFN-γ/HIF-1α/ glycolysis pathway. IL-36γ may be a potential treatment target and useful biomarker for tuberculosis.