Retracted: Leishmania infection activates host mTOR for its survival by M2 macrophage polarization
Retraction(s) for this article
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Retraction
- Volume 45Issue 1Parasite Immunology
- First Published online: November 28, 2022
Ajay Kumar
Division of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, Bihar, India
Search for more papers by this authorSushmita Das
Department of Microbiology, All India Institute of Medical Sciences, Patna, Bihar, India
Search for more papers by this authorAbhishek Mandal
Division of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, Bihar, India
Search for more papers by this authorSudha Verma
Division of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, Bihar, India
Search for more papers by this authorKumar Abhishek
Division of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, Bihar, India
Search for more papers by this authorAshish Kumar
Division of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, Bihar, India
Search for more papers by this authorVinod Kumar
Division of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, Bihar, India
Search for more papers by this authorAyan Kumar Ghosh
Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland
Search for more papers by this authorCorresponding Author
Pradeep Das
Division of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, Bihar, India
Correspondence
Pradeep Das, Division of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, Bihar, India.
Email: [email protected]
Search for more papers by this authorAjay Kumar
Division of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, Bihar, India
Search for more papers by this authorSushmita Das
Department of Microbiology, All India Institute of Medical Sciences, Patna, Bihar, India
Search for more papers by this authorAbhishek Mandal
Division of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, Bihar, India
Search for more papers by this authorSudha Verma
Division of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, Bihar, India
Search for more papers by this authorKumar Abhishek
Division of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, Bihar, India
Search for more papers by this authorAshish Kumar
Division of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, Bihar, India
Search for more papers by this authorVinod Kumar
Division of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, Bihar, India
Search for more papers by this authorAyan Kumar Ghosh
Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland
Search for more papers by this authorCorresponding Author
Pradeep Das
Division of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, Bihar, India
Correspondence
Pradeep Das, Division of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Patna, Bihar, India.
Email: [email protected]
Search for more papers by this authorFunding information
This work was carried out through the Intramural Project Program (INT-117-BAS/2015) of the Indian Council of Medical Research (I.C.M.R.) and funded by I.C.M.R. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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.
CONFLICT OF INTEREST
The authors declare no competing financial interests.
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