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

## TL;DR

This study explores how a tuberculosis protein influences macrophage behavior and how targeting a specific enzyme could help fight the infection.

## Contribution

The study identifies PKM2 as a novel target in M. tuberculosis-induced M2 macrophage polarization.

## Key findings

- PKM2 expression, activity, and nuclear translocation are impaired in Rv1987-induced M2 macrophages.
- Activation of PKM2 reverses M2 polarization and reduces mycobacterial load in mouse lungs.

## Abstract

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.

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.

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.

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.