Autophagy, Interleukin 27, mycobacterium, tuberculosis
presentationposted on 06.08.2018, 21:54 by gaurav sharmagaurav sharma
Interleukin-27 (IL-27), a key immunoregulatory cytokine plays an important role in host responseto mycobacterial infection as neutralization of IL-27 augments intracellular killing of mycobacteria.Autophagy has a pivotal role in host immunity and is regulated by various cytokines. Here, we report thatIL-27 inhibits IFN- and starvation induced autophagy and as a result blocks phagosome maturation andpromotes intracellular survival of Mycobacterium tuberculosis H37Rv. Addition of exogenous IL-27 inducesthe activation of mTOR through JAK/PI3 K pathway and inhibits IFN- stimulated autophagy. Further-more, blockade of JAKs obstructs the inhibitory effect of IL-27 on IFN- induced autophagy. Besides this,IL-27 also up-regulates Mcl-1through PI3 K pathway. We further show that in mTOR or Mcl-1 silencedTHP-1 cells, IL-27 could no longer inhibit IFN- mediated autophagy in M. tuberculosis H37Rv infectedcells. Altogether, our study demonstrates that IL-27 by concurrent activation of JAK/PI3 K/Akt/mTOR cas-cade as well as up-regulation of Mcl-1 inhibits IFN- induced autophagy and elimination of intracellularmycobacteria in macrophages.