Full length article Leptin induces the phagocytosis and protective immune response in Leishmania donovani infected THP-1 cell line and human PBMCs Alti Dayakar, Sambamurthy Chandrasekaran, Jalaja Veronica, Radheshyam Maurya * Department of Animal Biology, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad, 500 046, India highlights graphical abstract  Leptin induces L. donovani parasite uptake by macrophages of both THP- 1 and PBMCs.  Leptin upregulates the reactive oxy- gen species generation in infected THP-1.  Leptin enhances the phosphorylation of Akt and Erk1/2 signaling in infec- ted THP-1.  Leptin enhances the proin- flammatory cytokine response against L. donovani infection in both THP-1 and PBMCs. article info Article history: Received 27 July 2015 Received in revised form 5 October 2015 Accepted 7 December 2015 Available online 11 December 2015 Keywords: Leptin Visceral leishmaniasis Phagocytosis Proinflammatory response Reactive oxygen species abstract Visceral leishmaniasis (VL) is an infectious disease responsible for several deaths in malnourished children due to impaired cell-mediated immunity, which is accompanied by low circulating leptin levels. The cytokine function of leptin is implicated for several immune regulation activities such as hemato- poiesis, angiogenesis, innate and adaptive immunity. Its deficiency associated with polarization of Th2 response, which coincides with VL pathogenesis. To determine the cytokine role of leptin in case of experimental VL, we tested the leptin associated Th1/Th2 type cytokine profile at mRNA level from Leishmania donovani infected human monocytic leukemia cell line (THP-1) and peripheral blood mononuclear cells (PBMCs). We also tested the effect of leptin on macrophages activation (viz. studying the phosphorylation of signaling moieties), phagocytic activity and intracellular reactive oxygen species (ROS) production during infection. We observed that leptin induced Th1 specific response by upregu- lation of IL-1a, IL-1b, IL-8 and TNF-a in THP-1 and IFN-g, IL-12 and IL-2 in PBMCs. We also observed the downregulation of Th2 type cytokine i.e. IL-10 in THP-1 and unaltered expression of cytokines i.e. TGF-b, IL-10 and IL-4 in PBMCs. In addition, leptin stimulates the macrophages by inducing phosphorylation of Erk1/2 and Akt which are usually dephosphorylated in L. donovani infection. In concordance, leptin also induces the macrophage phagocytic activity by enhancing the intracellular ROS generation which helps in phagolysosome formation and oxidative killing of the parasite. In compilation, leptin is able to Abbreviations: VL, visceral leishmaniasis; THP-1, human monocytic leukemia cell line; PBMCs, peripheral blood mononuclear cells; ROS, reactive oxygen species; Erk1/2, extracellular-regulated kinase 1/2; Akt, protein kinase B; IL, interleukin; TNF-a, tumor necrosis factor-a; TGF-b, transforming growth factor-b; IFN-g, inter- feron-g; iNOS, inducible nitric oxide synthase; CD, cluster differentiation factor; MFI, mean fluorescence intensity; H 2 DCFDA, 2, 7- dichlorodihydrofluoresceindiacetate; RIPA, radioimmunoprecipitation assay. * Corresponding author. E-mail addresses: rmusl@uohyd.ernet.in, radhemaurya@rediffmail.com (R. Maurya). Contents lists available at ScienceDirect Experimental Parasitology journal homepage: www.elsevier.com/locate/yexpr http://dx.doi.org/10.1016/j.exppara.2015.12.002 0014-4894/© 2015 Elsevier Inc. All rights reserved. Experimental Parasitology 160 (2016) 54e59