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Title: Pattern recognition in Leishmania infection and its consequence on anti leishmanial immune response
Researcher: Srivastava, Sunit Kumar
Guide(s): Saha, Bhaskar
Keywords: Biochemical, Cell Science
Upload Date: 2-Sep-2011
University: University of Pune
Completed Date: October, 2008
Abstract: Toll-like receptors (TLR) recognize pathogen-expressed molecular patterns, signalthrough myeloid differentiation factor-88 (MyD88) inducing inflammatory cytokines and confer resistance against pathogens by mobilizing both innate and adaptive immune systems. Paradoxically, pathogens establish infection despite the presence of TLRs and MyD88 implying unknown TLR functions that can be a target of a novel pathogendevised immune evasion strategy. Therefore, we examined the expression and function of TLRs in Leishmania infection, which occurs in 12 million people annually. We demonstrate that TLR1, TLR11 and TLR12 expressions are up-regulated whereas TLR4 and TLR9 expressions are down regulated in BALB/c-derived Leishmania majorinfected macrophages that play host to the parasite. Leishmania-expressed lipophosphoglycan (LPG), a virulence factor and a TLR2-ligand, appears necessary for the reciprocal regulation of these TLRs. Another synthetic TLR2-ligand, peptidoglycan (PGN) recapitulates the LPG effects. Pam3CSK4 and profilin, the respective ligands for TLR1 and TLR11, induce higher IL-10 whereas lipopolysaccharide and CpG, the ligands for TLR4 and TLR9 respectively, induce higher IL-12 productions. Pam3CSK4 and profilin inhibit the CpG-induced IL-12 production from macrophages perhaps by reducing TLR9 expression. Pam3CSK4 administration enhances L. major infection and their disease progression ability can be inhibited by neutralizing IL-10 and addition of rIL-12.Thus, the pathogen-devised TLR2-targeted immune evasion strategy and the trans-TLR regulation through a complex network of TLRs imply a novel role for TLRs in the immuno-regulatory framework.
Pagination: 107p.
Appears in Departments:National Centre for Cell Science

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02_certificate.pdf29.85 kBAdobe PDFView/Open
03_declaration.pdf30.72 kBAdobe PDFView/Open
04_acknowledgements.pdf30.56 kBAdobe PDFView/Open
05_index.pdf10.25 kBAdobe PDFView/Open
06_abbreviations.pdf74.04 kBAdobe PDFView/Open
07_abstract.pdf113.81 kBAdobe PDFView/Open
08_genesis of thesis.pdf134.48 kBAdobe PDFView/Open
09_chapter 1.pdf1.06 MBAdobe PDFView/Open
10_chapter 2.pdf139.53 kBAdobe PDFView/Open
11_chapter 3.pdf161.33 kBAdobe PDFView/Open
12_chapter 4.pdf822.76 kBAdobe PDFView/Open
13_chapter 5.pdf147.49 kBAdobe PDFView/Open
14_chapter 5.pdf129.57 kBAdobe PDFView/Open
15_bibliography.pdf203.72 kBAdobe PDFView/Open
16_publications.pdf5.27 MBAdobe PDFView/Open

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