In:
Parasite Immunology, Wiley, Vol. 40, No. 11 ( 2018-11)
Abstract:
Mammalian target of rapamycin (m TOR ) 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 m TOR pathway characterized by phosphorylation of m TOR , 70S6K and 4‐ EBP 1. Inhibition of m TOR 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‐ RPS 6. m TOR 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, CD 206 and CD 163). Furthermore, we observed that in case of Leishmania infection, m TOR 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 m TOR plays a crucial role in regulation of M2 macrophage polarization and direct the innate immune homeostasis towards parasite survival inside host.
Type of Medium:
Online Resource
ISSN:
0141-9838
,
1365-3024
DOI:
10.1111/pim.2018.40.issue-11
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2020808-X
SSG:
12
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