Elucidation of the Signaling Mechanisms Involved in the Subversion of Host Immune Response by Intracellular Parasite Leishmania Donovani
EPrints@IICB
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Title |
Elucidation of the Signaling Mechanisms Involved in the Subversion of Host Immune Response by Intracellular Parasite Leishmania Donovani |
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Creator |
Srivastav, Supriya
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Subject |
Infectious Diseases and Immunology
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Description |
The intracellular parasite L. donovani has the unique capacity to survive and replicate inside host macrophages. Since this cell type is specialized for the destruction of invading pathogens and priming of the host immune response, Leishmania has had to evolve a range of sophisticated mechanisms to subvert normal macrophage function. This enables the parasite to evade the innate immune response and to divide within the phagolysosome of the infected macrophage, from where it can spread and propagate the disease within the host. There are multiple ways by which intracellular pathogens like Leishmania make use of host cell’s machinery in order to survive and replicate. One such mechanism is the distortion of host macrophage’s own signaling pathways to selectively repress or enhance the expression of various cytokines and microbicidal molecules and antigen presentation. Within the scope of this work, an attempt has been made to focus on the molecular mechanisms by which Leishmania can subvert host immune surveillance by altering the macrophage signal transduction machinery, thereby modulating the macrophage environment in its favour. Toll-like receptors (TLRs), which form an interface between mammalian host and microbe, play a key role in pathogen recognition and initiation of pro-inflammatory response thus stimulating antimicrobial activity and host survival. However, certain intracellular pathogens like Leishmania, can successfully manipulate the TLR signaling, thus hijacking the defensive strategies of the host. Despite the presence of lipophosphoglycan (LPG), a TLR2 ligand capable of eliciting host-defensive cytokine response, on the surface of Leishmania, the strategies adopted by the parasite to silence the TLR2-mediated pro-inflammatory response is not understood. Although the ability of Leishmania to inhibit inflammatory signaling pathways has been proposed as a virulence mechanism, the molecular events underlying this process remain still to be explored. The aim of this study was to determine the mechanism used by Leishmania to modulate TLR signaling cascade for its own favor. |
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Date |
2012
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Type |
Thesis
NonPeerReviewed |
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Format |
application/pdf
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Identifier |
http://www.eprints.iicb.res.in/1802/1/THESIS.pdf
Srivastav, Supriya (2012) Elucidation of the Signaling Mechanisms Involved in the Subversion of Host Immune Response by Intracellular Parasite Leishmania Donovani. PhD thesis, Calcutta University. |
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Relation |
http://www.eprints.iicb.res.in/1802/
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