title: Identification and functional characterization of Leishmania donovani secretory peroxidase: delineating its role in NRAMP1 regulation.
abstract: Leishmania silently evades host immune system and establish in the hostile environment of host macrophage phagolysosomes. For differentiation, growth and division parasite acquires divalent cations especially iron from the host nutritive pool. Natural resistance associated with macrophage protein1 (NRAMP1), a cation transporter that effluxes out divalent cations specifically iron from phagosomal milieu to the cytosol, to create ions deprived status for pathogenic microorganisms. The mechanisms of NRAMP1 regulation are largely unknown in leishmanial infections. In the present study, we identified a secretory Leishmania donovani peroxidase (Prx) that showed peroxidoxin like peroxidase activity and significantly reduced H(2)O(2), O(2).(-) and NO levels in LPS activated macrophages. Further, we also observed down regulated Nramp1 expression and concomitantly declined labile iron pool in activated macrophages treated with identified peroxidase. Prx also decreased levels of TNF-α, IFN-γ and IL-12 in LPS activated macrophages. These observations indicate a bifunctional protective role of secretory Prx; first it reduces redox activation of macrophages, and secondly it allows iron access to Leishmania by down regulating NRAMP1 expression.
authors: Molecular Immunology Laboratory, Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi, India.
authors: Nisha
authors: N
authors: Singh
authors: Surabhi
authors: S
authors: Bajpai
authors: Vinod
authors: V
authors: Kumar
authors: Jalaj K
authors: JK
authors: Gour
authors: Rakesh K
authors: RK
authors: Singh
mesh_terms: D000818:Animals; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D007893:Leishmania donovani / Q000201:enzymology*; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009195:Peroxidase / Q000737:chemistry / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D015398:Signal Transduction; D016622:Silver Staining; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D016207:Cytokines; D006861:Hydrogen Peroxide; D009566:Nitrates; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites; D009195:Peroxidase; D010744:Phosphoric Monoester Hydrolases; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D013481:Superoxides; D000099173:Natural Resistance-associated Macrophage Protein 1