TLR4 and NKT Cell Synergy in Immunotherapy against Visceral Leishmaniasis
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
TLR4 and NKT Cell Synergy in Immunotherapy against
Visceral Leishmaniasis
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| Creator |
Karmakar, Subir
Bhaumik, Siddhartha Kumar Paul, Joydeep De, Tripti |
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| Subject |
Infectious Diseases and Immunology
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| Description |
NKT cells play an important role in autoimmune diseases, tumor surveillance, and infectious diseases, providing in most
cases protection against infection. NKT cells are reactive to CD1d presented glycolipid antigens. They can modulate immune
responses by promoting the secretion of type 1, type 2, or immune regulatory cytokines. Pathogen-derived signals to
dendritic cells mediated via Toll like Receptors (TLR) can be modulated by activated invariant Natural Killer T (iNKT) cells. The
terminal b-(1–4)-galactose residues of glycans can modulate host responsiveness in a T helper type-1 direction via IFN-c and
TLRs. We have attempted to develop a defined immunotherapeutic, based on the cooperative action of a TLR ligand and
iNKT cell using a mouse model of visceral leishmaniasis. We evaluated the anti-Leishmania immune responses and the
protective efficacy of the b-(1–4)-galactose terminal NKT cell ligand glycosphingophospholipid (GSPL) antigen of L. donovani
parasites. Our results suggest that TLR4 can function as an upstream sensor for GSPL and provoke intracellular inflammatory
signaling necessary for parasite killing. Treatment with GSPL was able to induce a strong effective T cell response that
contributed to effective control of acute parasite burden and led to undetectable parasite persistence in the infected
animals. These studies for the first time demonstrate the interactions between a TLR ligand and iNKT cell activation in
visceral leishmaniasis immunotherapeutic.
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| Date |
2012
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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/1543/1/PLOS_PATHOGENS___8(_4);2012[22].pdf
Karmakar, Subir and Bhaumik, Siddhartha Kumar and Paul, Joydeep and De, Tripti (2012) TLR4 and NKT Cell Synergy in Immunotherapy against Visceral Leishmaniasis. PLoS Pathogens, 8 (4). e1002646. |
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| Relation |
http://dx.doi.org/:10.1371/journal.ppat.1002646
http://www.eprints.iicb.res.in/1543/ |
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