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Leishmania donovani: CD2 biased immune response skews the SAG mediated therapy for a predominant Th1 response in experimental infection.
- Source :
-
Experimental parasitology [Exp Parasitol] 2012 Jul; Vol. 131 (3), pp. 274-82. Date of Electronic Publication: 2012 May 10. - Publication Year :
- 2012
-
Abstract
- We have evaluated the effect of combining CD2 with conventional antimonial (sb) therapy in protection in BALB/c mice infected with either drug sensitive or resistant strain of Leishmania donovani with 3×10(7) parasites via-intra-cardiac route. Mice were treated with anti CD2 adjunct SAG sub-cutaneously twice a week for 4 weeks. Assessment for measurement of weight, spleen size, anti-Leishmania antibody titer, T cell and anti-leishmanial macrophage function was carried out day 0, 10, 22 and 34 post treatments. The combination therapy was shown boosting significant proportion of T cells to express CD25 compared to SAG monotherapy. Although, the level of IFN-γ was not statistically different between combination vs monotherapy (p=0.298) but CD2 treatment even alone significantly influenced IFN-γ production than either SAG treatment (p=0.045) or with CD2 adjunct SAG treatment (p=0.005) in Ld-S strain as well as in Ld-R strain. The influence of CD2 adjunct treatment was also documented in anti-leishmanial functions in macrophages. As shown, the super-oxide generation began enhancing very early on day 10 after SAG treatment with CD2 during which SAG action was at minimum. Interestingly, the super-oxide generation ability remained intact in macrophage after treatment with immuno-chemotherapy even in mice infected with Leishmania resistant strain. Unlike SAG treatment, treatment of SAG with CD2 also led to production of nitric oxide and TNF-α, resulting in resulting in most effective clearance of L. donovani from infected macrophages. Our results indicate that CD2, which can boost up a protective Th1 response, might also be beneficial to enable SAG to induce Macrophages to produce Leishmanicidal molecules and hence control the infection in clinical situation like Kala-azar. Drug resistance is the major impedance for disease control but the encouraging results obtained after infecting mice with resistant strain of the parasite strongly imply that this drug can be effective even in treating resistant cases of Kala-azar.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antibodies, Monoclonal immunology
Antibodies, Monoclonal therapeutic use
Drug Resistance
Drug Therapy, Combination
Humans
Immunologic Factors immunology
Immunologic Factors therapeutic use
Interferon-alpha metabolism
Leishmania donovani drug effects
Leishmaniasis, Visceral drug therapy
Leishmaniasis, Visceral prevention & control
Leukocytes, Mononuclear immunology
Macrophages immunology
Macrophages metabolism
Macrophages parasitology
Mice
Mice, Inbred BALB C
Nitric Oxide metabolism
Prospective Studies
Respiratory Burst
Spleen cytology
Spleen immunology
Superoxides metabolism
Tumor Necrosis Factor-alpha metabolism
Antimony Sodium Gluconate therapeutic use
Antiprotozoal Agents therapeutic use
CD2 Antigens immunology
Leishmania donovani immunology
Leishmaniasis, Visceral immunology
Th1 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2449
- Volume :
- 131
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Experimental parasitology
- Publication Type :
- Academic Journal
- Accession number :
- 22580024
- Full Text :
- https://doi.org/10.1016/j.exppara.2012.04.007