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Leishmania infection activates host mTOR for its survival by M2 macrophage polarization.
- Source :
- Parasite Immunology; Nov2018, Vol. 40 Issue 11, pN.PAG-N.PAG, 1p
- Publication Year :
- 2018
-
Abstract
- Summary: Mammalian target of rapamycin (mTOR) is a central regulator of growth and immunity of host cells. It's involvement in cancer and tuberculosis is well documented but least explored in Leishmania donovani invasion of host cells. Therefore, in the present study, we aimed to investigate the role of mTOR in M2 macrophage polarization for Leishmania survival. We observed that Leishmania infection activated host mTOR pathway characterized by phosphorylation of mTOR, 70S6K and 4‐EBP1. Inhibition of mTOR resulted in decreased parasite load and percent infectivity. Moreover, Leishmania infection triggered cell proliferation as was evidenced by increased expression of cyclin A and p‐RPS6. mTOR activation during Leishmania infection resulted in reduced expression of M1 macrophage markers (eg, ROS, NO, iNOS, NOX‐1, IL‐12, IL‐1β and TNF‐α), and increased expression of M2 macrophage markers (eg, arginase‐1, IL‐10, TGF‐β, CD206 and CD163). Furthermore, we observed that in case of Leishmania infection, mTOR inhibition increased the translocation of NF‐κB to nucleus and deactivation of STAT‐3. Eventually, we observed that inhibition of M2 macrophage polarization reduced Leishmania survival inside macrophages. Therefore, our findings suggest that mTOR plays a crucial role in regulation of M2 macrophage polarization and direct the innate immune homeostasis towards parasite survival inside host. [ABSTRACT FROM AUTHOR]
- Subjects :
- LEISHMANIA
MTOR protein
MACROPHAGES
CELL proliferation
IMMUNE response
THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 01419838
- Volume :
- 40
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- Parasite Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 132313087
- Full Text :
- https://doi.org/10.1111/pim.12586