Effect of PKM2 onRv1987-induced macrophage M2 polarization.

Abstract

INTRODUCTION: Mycobacteria induce host macrophage M2 polarization to construct a kindly environment for their intracellular growth. In our previous study, we found thatRv1987 protein induced macrophage polarization to M2-like phenotype. However, little is known about the changes of host metabolites and the effects of related enzymes in this process. METHODS: Here, using our previously constructed infection model byoverexpressing Rv1987 protein, we analyzed the alterations of energy metabolism-related metabolites and the function of M2 isoform of pyruvate kinase (PKM2), the key enzyme of glycolysis, in mycobacteria-induced M2 macrophages. RESULTS: The results showed that the expression, enzyme activity and nucleus translocation of PKM2 were all impaired in Rv1987-induced M2 macrophages. Activation of PKM2 by its activator TEPP-46 reversed the M2 polarization and enhanced the inflammation of macrophages, and subsequently reduced the mycobacterial load in mouse lung tissues during infection. CONCLUSION: All these results suggested that host PKM2 is closely associated withRv1987-induced M2 polarization, which can be considered as an intervention target in anti-tuberculosis therapy.