Potassium ion channel Kir2.1 negatively regulates protective responses to Mycobacterium bovis BCG.

Tuberculosis caused by the pathogen Mycobacterium tuberculosis leads to increased mortality and morbidity worldwide. The prevalence of highly drug-resistant strains has reinforced the need for greater understanding of host-pathogen interactions at the cellular and molecular levels. Our previous work demonstrated critical roles of calcium ion channels in regulating protective responses to mycobacteria. In this report, we deciphered the roles of inwardly rectifying K⁺ ion channel K_ir2.1 in epithelial cells. Data showed that infection of epithelial cells (and macrophages) increases the surface expression of K_ir2.1. This increased expression of K_ir2.1 results in higher intracellular mycobacterial survival, as either inhibiting or knocking down K_ir2.1 results in mounting of a higher oxidative burst leading to a significant attenuation of mycobacterial survival. Further, inhibiting K_ir2.1 also led to increased expression of T cell costimulatory molecules accompanied with increased activation of MAP kinases and transcription factors nuclear factor κB and phosphorylated CREB. Furthermore, inhibiting K_ir2.1 induced increased autophagy and apoptosis that could also contribute to decreased bacterial survival. Interestingly, an increased association of heat shock protein 70 kDa with K_ir2.1 was observed. These results showed that mycobacteria modulate the expression and function of K_ir2.1 in epithelial cells to its advantage. [ABSTRACT FROM AUTHOR]