Targeting of immunostimulatory DNA cures experimental visceral leishmaniasis through nitric oxide up-regulation and T cell activation
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Targeting of immunostimulatory DNA cures
experimental visceral leishmaniasis through nitric
oxide up-regulation and T cell activation
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| Creator |
Datta, Neeta
Mukherjee, Snigdha Das, Lopamudra Das, Pijush K |
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| Subject |
Infectious Diseases and Immunology
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| Description |
Active targeting of CpG-containing oligodeoxynucleotide (CpG-ODN) to macrophages was
studied by incorporating it in mannose-coated liposomes, using visceral leishmaniasis as
the model macrophage disease. Mannosylated liposomal CpG-ODN was more effective
than liposomal or free CpG-ODN in inhibiting amastigote multiplication within macrophages.
Moreover, in a 60-day mouse model of visceral leishmaniasis, complete elimination of spleen
parasite burden was achieved by mannosylated liposomal CpG-ODN, compared to 62%
and 81% parasite suppression by free and liposomal ODN, respectively, at a similar dose.
Although in vitro exposure of CpG-ODN did not induce marked nitric oxide (NO) generation
by macrophages, considerably enhanced amount of NO was generated by macrophages of
CpG-ODN-treated animals. Their splenocytes secreted soluble factors required for the
induction of NO generation, and the increased NO generation was paralleled by an increase
in antileishmanial activity. Inducible NO generation was suppressed by treating splenocyte
supernatants with anti-IFN- + or anti-IL-12 antibodies, whereas in vivo administration of
these anti-cytokine Ab along with CpG-ODN reversed protection against infection. CpGODN
treatment resulted in reduced levels of IL-4, but increased levels of IFN- + , IL-12 and
inducible NO synthase in infected spleen cells, which was magnified by encapsulation in
mannose-coated liposomes. This targeted treatment was not only curative, but it also
imparted resistance to reinfection. These results represent a general approach for intracellular
targeting of CpG-ODN, which effectively enhances its therapeutic potential in redirecting
curative Th1 responses in Th2-driven disorders.
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| Date |
2003
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/558/1/EUROPEAN_JOURNAL_OF_IMMUNOLOGY%2C_33(_6)%2C_1508%2D1518[56].pdf
Datta, Neeta and Mukherjee, Snigdha and Das, Lopamudra and Das, Pijush K (2003) Targeting of immunostimulatory DNA cures experimental visceral leishmaniasis through nitric oxide up-regulation and T cell activation. European Journal of Immunology, 33 (6). pp. 1508-1518. |
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| Relation |
http://dx.doi.org/10.1002/eji.200323671
http://www.eprints.iicb.res.in/558/ |
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