115 kDa serine protease confers sustained protection to visceral leishmaniasis caused by Leishmania donovani via IFN-�Y induced down-regulation of TNF-� mediated MMP-9 activity
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
115 kDa serine protease confers sustained protection to visceral leishmaniasis caused by Leishmania donovani via IFN-�Y induced down-regulation of TNF-� mediated MMP-9 activity
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| Creator |
Choudhury, Rajdeep
Das, Partha De, Tripti Chakraborti, Tapati |
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| Subject |
Infectious Diseases and Immunology
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| Description |
Visceral leishmaniasis caused by the intracellular parasite Leishmania donovani is a major public health
problem in the developing world. The emergence of increasing number of L. donovani strains resistance
to antimonial drugs recommended worldwide requires the intervention of effective vaccine strategy for
treatment of VL. In the present study L. donovani culture derived, soluble, secretory serine protease (pSP)
has been shown to be vaccine target of VL. Protection from VL could be achieved by the use of safer
vaccine which generally requires an adjuvant for induction of strong Th1 response. To assess the safety,
immunogenicity and efficacy of pSP as vaccine candidate in mouse model we used IL-12 as adjuvant.
BALB/c mice immunized with pSP+IL-12 were protected significantly from challenged infection even after
four months by reducing the parasite load in liver and spleen and suppressed the development of the
disease along with an increase in IgG2a antibody level in serum, enhanced delayed type hypersensitivity
and strong T-cell proliferation. Groups receiving pSP+IL-12 had an augmented pSP antigen specific Th1
cytokines like IFN-� and TNF-� response with concomitant decrease of Th2 cytokines IL-4 and IL-10 after
vaccination. In this study the vaccine efficacy of pSP was further assessed for its prophylactic potential by
enumerating matrix metalloprotease-9 (MMP-9) profile which has been implicated in various diseases.
MMP-9 associated with different microbial infections is controlled by their natural inhibitors (TIMPS) and
by some cytokines. In this study pSP was found to regulate excessive inflammation by modulating the
balance between MMP-9 and TIMP-1 expression. This modulatory effect has also been demonstrated by
IFN-� mediated down regulation of TNF-� induced MMP-9 expression in activated murine macrophages.
This is the first report where a secretory L. donovani serine protease (pSP) adjuvanted with IL-12 could
also act as protective imunogen by modifying cytokine mediated MMP-9 expression in experimental VL.
These findings elucidate the mechanisms of regulation of MMP-9 following infection of L. donovani in
vaccinated animals and thus pave the way for developing new immunotherapeutic interventions for VL.
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| Publisher |
Elsevier
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| Date |
2013
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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/1963/1/IMMUNOBIOLOGY__Volume_218__(_1)114%2D126_;2013[139].pdf
Choudhury, Rajdeep and Das, Partha and De, Tripti and Chakraborti, Tapati (2013) 115 kDa serine protease confers sustained protection to visceral leishmaniasis caused by Leishmania donovani via IFN-�Y induced down-regulation of TNF-� mediated MMP-9 activity. Immunobiology, 218 (1). pp. 114-126. |
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| Relation |
http://dx.doi.org/10.1016/j.imbio.2012.02.008
http://www.eprints.iicb.res.in/1963/ |
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