41 research outputs found
Selective killing of Mycobacterium avium-infected macrophages by inhibition of phosphorylated signal transducer and activator of transcription type 1
Mycobacterium avium infects mononuclear phagocytes,
which thereby become reservoirs for this pathogen. Currently
recommended therapy does not ensure the eradication of intracellular
bacteria. Here, we report that M. avium infection in
macrophages activates the signal transducer and activator of
transcription type 1 (STAT-1) signaling pathway. Fludarabine,
an antileukemic drug active against cells that express
STAT-1, selectively kills M. avium–infected macrophages.
These findings suggest that phosphorylated STAT-1 can enhance
the survival of macrophages, promoting their role as
persistent reservoirs of M. avium. This work invites research
on new combination therapeutic approaches that consist of
fludarabine, to kill the macrophage reservoir, and antibacterial
agents, to eliminate mycobacteria released from the dead
cells