title: Treatment with IP-10 induces host-protective immune response by regulating the T regulatory cell functioning in Leishmania                      donovani-infected mice.
abstract: Visceral leishmaniasis (VL), caused by the protozoan parasite, Leishmania donovani, is characterized by an infection in the liver and spleen. The failure of the first-line drugs has led to the development of new strategies for combating VL. Recently, our group has shown that interferon-γ-inducible protein (IP)-10, a CXC chemokine, renders protection against VL. In the present study, we have elucidated the mechanism by which IP-10 renders protection in in vivo L. donovani infection. We observed that IP-10-treated parasitized BALB/c mice showed a strong host-protective T helper cell (Th) 1 immune response along with marked decrease in immunosuppressive cytokines, tumor growth factor (TGF)-β, and interleukin (IL)-10 secreting CD4(+) T cells. This IP-10-mediated decrease in immunosuppressive cytokines was correlated with the reduction in the elevated frequency of CD4(+)CD25(+) T regulatory (Treg) cells along with the reduced TFG-β production from these Treg cells in Leishmania-infected mice. This reduction in TGF-β production was due to effective modulation of TGF-β signaling by IP-10, which reduced the immunosuppressive activity of Treg cells. Thus, these findings put forward a detailed mechanistic insight into IP-10-mediated regulation of the Treg cell functioning during experimental VL, which might be helpful in combating Leishmania-induced pathogenesis.
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Gupta
authors.forename: Saikat
authors.initials: S
authors.lastname: Majumdar
authors.forename: Anupam
authors.initials: A
authors.lastname: Adhikari
authors.forename: Parna
authors.initials: P
authors.lastname: Bhattacharya
authors.forename: Asok Kumar
authors.initials: AK
authors.lastname: Mukherjee
authors.forename: Suchandra Bhattacharyya
authors.initials: SB
authors.lastname: Majumdar
authors.forename: Subrata
authors.initials: S
authors.lastname: Majumdar
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology; D049109:Cell Proliferation; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000008:administration & dosage / Q000494:pharmacology*; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology; D004149:Dioxoles / Q000008:administration & dosage / Q000494:pharmacology; D005434:Flow Cytometry; D007111:Immunity, Cellular; D007893:Leishmania donovani / Q000276:immunology* / Q000472:pathogenicity; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000469:parasitology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D015398:Signal Transduction; D051901:Smad4 Protein / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D000981:Antiprotozoal Agents; D001549:Benzamides; D054357:Chemokine CXCL10; D016207:Cytokines; D004149:Dioxoles; D051901:Smad4 Protein; C490810:Smad4 protein, mouse