title: Leptin induces the phagocytosis and protective immune response in Leishmania donovani infected THP-1 cell line and human PBMCs.
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 hematopoiesis, 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 upregulation of IL-1α, IL-1β, IL-8 and TNF-α in THP-1 and IFN-γ, 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-β, 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 maintain the defensive environment against L. donovani infection through the classical macrophage activity.
authors.affiliation: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad, 500 046, India.
authors.forename: Alti
authors.initials: A
authors.lastname: Dayakar
authors.affiliation: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad, 500 046, India.
authors.forename: Sambamurthy
authors.initials: S
authors.lastname: Chandrasekaran
authors.affiliation: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad, 500 046, India.
authors.forename: Jalaja
authors.initials: J
authors.lastname: Veronica
authors.affiliation: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad, 500 046, India. Electronic address: rmusl@uohyd.ernet.in.
authors.forename: Radheshyam
authors.initials: R
authors.lastname: Maurya
mesh_terms: D045744:Cell Line, Tumor; D016207:Cytokines / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000517:prevention & control; D020738:Leptin / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000469:parasitology*; D009504:Neutrophils / Q000276:immunology / Q000469:parasitology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D020738:Leptin; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D052247:Nitric Oxide Synthase Type II; D051057:Proto-Oncogene Proteins c-akt
keywords: Leptin; Phagocytosis; Proinflammatory response; Reactive oxygen species; Visceral leishmaniasis