Effect of PKM2 on M. tuberculosis Rv1987-induced macrophage M2 polarization.

INTRODUCTION

Mycobacteria induce host macrophage M2 polarization to construct a kindly environment for their intracellular growth. In our previous study, we found that M. tuberculosis Rv1987 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 by M. smegmatis overexpressing 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 with M. tuberculosis Rv1987-induced M2 polarization, which can be considered as an intervention target in anti-tuberculosis therapy.