Dendritic cell-based immunotherapy combined with antimony-based chemotherapy cures established murine visceral leishmaniasis.
Dendritic cells (DCs) have been proposed to play a critical role as adjuvants in vaccination and immunotherapy. In this study we evaluated the combined effect of soluble Leishmania donovani Ag (SLDA)-pulsed syngeneic bone marrow-derived DC-based immunotherapy and antimony-based chemotherapy for the treatment of established murine visceral leishmaniasis. Three weekly injections of SLDA-pulsed DCs into L. donovani-infected mice reduced liver and splenic parasite burden significantly, but could not clear parasite load from these organs completely. Strikingly, the conventional antileishmanial chemotherapy (sodium antimony gluconate) along with injections of SLDA-pulsed DCs resulted in complete clearance of parasites from both these organs. Repetitive in vitro stimulation of splenocytes from uninfected or L. donovani-infected mice with SLDA-pulsed DCs led to the emergence of CD4(+) T cells with characteristics of Th1 cells. Our data indicate that DC-based immunotherapy enhances the in vivo antileishmanial potential of antimony or vice versa.
Ghosh
Monidipa
M
Division of Immunology, Indian Institute of Chemical Biology, Jadavpur, Kolkata, India.
Pal
Chiranjib
C
Ray
Mitali
M
Maitra
Sudipta
S
Mandal
Labanya
L
Bandyopadhyay
Santu
S
D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000469:parasitology / Q000637:transplantation; D000953:Antigens, Protozoan / Q000627:therapeutic use; D000965:Antimony / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology / Q000469:parasitology / Q000637:transplantation*; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007893:Leishmania donovani / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D016052:Protozoan Vaccines / Q000276:immunology / Q000627:therapeutic use*; D012995:Solubility; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000469:parasitology
D000953:Antigens, Protozoan; D000981:Antiprotozoal Agents; D016052:Protozoan Vaccines; D000965:Antimony