title: Therapy with radio-attenuated vaccine in experimental murine visceral leishmaniasis showed enhanced T cell and inducible nitric oxide synthase levels, suppressed tumor growth factor-beta production with higher expression of some signaling molecules.
abstract: BACKGROUND
  Visceral leishmaniasis (VL) or Kala-Azar (KA) is one of the most deadly forms of disease among all neglected tropical diseases. There are no satisfactory drugs or vaccine candidates available for this dreaded disease. Our previous studies showed promising therapeutic and prophylactic efficacy of the live, radio-attenuated parasites through intramuscular (I.M.) and intraperitoneal (I.P.) route in BALB/c mice model.
  
  
  METHODS
  The T-cell proliferation level, the mRNA expression level of inducible nitric oxide synthase (iNOS) and tumor growth factor-beta (TGF-β) genes and finally the phosphorylation levels of phosphoinositide dependent kinase 1 (PDK1), phosphoinositide 3 kinase (PI3K) and p38 mitogen activated protein kinase (p38MAPK) molecules were checked in BALB/c mice model immunized with radio-attenuated Leishmania donovani parasites through I.M. route.
  
  
  RESULTS
  Higher T-cell proliferation, increased iNOS level, and suppressed TGF-β level were found in treated infected animal groups (100 and 150Gy) in relation to untreated infected animals. Likewise, phosphorylation levels of PDK1, PI3K and p38MAPK of these two groups were increased when compared to untreated infected controls.
  
  
  CONCLUSIONS
  The clearance of the parasites from treated infected groups of animals may be mediated by the restoration of T-cell due to therapy with radio-attenuated L. donovani parasites. The killing of parasites was mediated by increase in nitric oxide release through PDK1, PI3K and p38MAPK signaling pathways. A lower TGF-β expression has augmented the restored Th1 ambience in the 100 and 150Gy treated animal groups proving further the efficacy of the candidate vaccine.
authors.affiliation: Post Graduate Department of Zoology, Barasat Government College, Kolkata, India.
authors.forename: Sanchita
authors.initials: S
authors.lastname: Datta
authors.affiliation: Infectious Diseases and Immunology, Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: Syamal
authors.initials: S
authors.lastname: Roy
authors.affiliation: Post Graduate Department of Zoology, Barasat Government College, Kolkata, India. Electronic address: madhumita.manna09@gmail.com.
authors.forename: Madhumita
authors.initials: M
authors.lastname: Manna
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D054332:Leishmaniasis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000517:prevention & control; D008297:Male; D008807:Mice, Inbred BALB C; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D059208:Parasite Load; D010766:Phosphorylation; D012333:RNA, Messenger; D018417:Th1 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics
chemical_list: D054332:Leishmaniasis Vaccines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014613:Vaccines, Attenuated; D052247:Nitric Oxide Synthase Type II; D064413:3-Phosphoinositide-Dependent Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: PDK1; PI3K; Radio-attenuated Leishmania parasites; p38MAPK