Complete protection against experimental visceral leishmaniasis with complete soluble antigen from attenuated Leishmania donovani promastigotes involves Th1-immunity and down-regulation of IL-10.
Compared with cutaneous leishmaniasis, vaccination against visceral leishmaniasis has received limited attention. Most available drugs are toxic, and relapse after cure remains a chronic problem. Growing limitations in available chemotherapeutic strategies due to emerging resistant strains and lack of an effective vaccine strategy against visceral leishmaniasis deepens the crisis. Complete soluble antigen (CSA), from a beta1-4 galactosyltransferase expressing attenuated Leishmania donovani parasite, induced protection against subsequent challenge and during active infections. CSA immunization was effective against both pentavalent antimony sensitive and resistant strains of L. donovani. Majority ( approximately 85%) of the immunized animals showed sterile protection. Resolution of the disease required the presence of T cells, and the recovered animals remained immune to re-challenge. Control of the parasites was dependent on type 1 CD4(+) helper cells, which evolved in the presence of IL-12 and activated macrophages through the production of IFN-gamma. Immunity was adoptively transferable and was dependent on both CD4(+) and CD8(+) cells. CSA immunization led to enhanced IFN-gamma production, while suppressing the IL-10 production. However, CSA immunization did not abrogate IL-4 production. Our results accentuate the need to establish a favorable cellular immunity while intervening with the development of Th2 cells during leishmania infection.
Bhaumik
Siddhartha Kumar
SK
Division of Infectious Disease and Immunology, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, Kolkata, India.
Naskar
Kshudiram
K
De
Tripti
T
D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology*; D017635:Clonal Anergy / Q000276:immunology; D006224:Cricetinae; D016207:Cytokines / Q000235:genetics; D015536:Down-Regulation; D015870:Gene Expression; D007114:Immunization / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism*; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D008109:Liver Diseases, Parasitic / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology / Q000469:parasitology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
D000953:Antigens, Protozoan; D016207:Cytokines; D015847:Interleukin-4; D007371:Interferon-gamma