Host-Parasite Interaction: Modulation of Signaling Pathways in Macrophage and Leishmania and its Impact on Parasite Infectivity
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Host-Parasite Interaction: Modulation of Signaling
Pathways in Macrophage and Leishmania and its
Impact on Parasite Infectivity
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| Creator |
Biswas, Arunima
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| Subject |
Cell Biology & Physiology
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| Description |
The life cycle of Leishmania is unique in terms of the extent of physiological, biochemical and
structural remodeling that occur during differentiation of procyclic promastigotes to metacyclic
promastigotes and metacycilc promastigotes to intracellular amastigotes. This human parasite
encounters tremendous oxidative burst during macrophage invasion along with a striking shift of
temperature and pH (22°C and pH 7.2 in the insect gut to 37°C and pH 5.5 in the parasitophorous
vacuole of macrophages). Though macrophages play indispensable role in producing cytokines
and chemokines and also activate other inflammatory cells to combat intracellular parasite infections,
parasites like Leishmania can impair these activities by taking advantage of the host antiinflammatory
response to avoid self-damage by modulating its own biology and host environment
and a subset of parasite persist successfully inside the host finally leading to disease manifestations.
Though macrophage biology is well studied, the molecular mechanism by which the parasites
circumvent the toxic effects of these reactive oxygen species is not fully understood. Studies
showed that some Leishmania molecules implicated in anti-oxidant defense by genes like superoxide
dismutase (SOD), peroxidoxin, trypanothione reductase and disruption of these genes or
transfection with trans-dominant inactive counterparts render the parasite more susceptible to
intracellular killing. The ability of Leishmania parasite to resist oxidative stress seems to be coupled
with their transformation and there must be some environmental sensing pathway which would
trigger the differentiation. Though in closely related kinetoplastida species Trypanosoma, cAMP
has been associated with differentiation, most of the studies regarding cAMP response in Leishmania
are confined within cloning and characterization of genes associated with cAMP response
and no in-depth study regarding the functional participation of these proteins with cellular differentiation
and infectivity of the parasite has been taken care of. In our previous study, cAMP
response has been implicated as one of the major environmental sensing machineries associated
with stress response in Leishmania (Bhattacharya et al., 2008). The multitudinous functions of
cAMP require precise spatial and temporal control of its production, degradation and detection.
Though novel proteins have been recently identified that critically modulate cAMP signal in several
organisms, not much is known about cAMP signaling in Leishmania. We sought to focus on
the molecular mechanisms whereby the Leishmania parasites can subvert host surveillance by
activating its own antioxidant machineries by cAMP mediated signaling. We here focus on the
control of the production of cAMP by receptor adenylate cyclase and whether the total pyrophosphate
pool, which is already known to be an environmental sensor in bacteria could control
the intracellular cAMP and sought to discuss the role of different cAMP-dependent phosphodiesterases
in modulating the cAMP signaling in the parasite. Lastly, within the scope of this work,
an attempt has been made to decipher how cAMP signaling grossly affects the parasite to exploit
host machineries like modulation of some important enzymes like arginase and whether we could
develop some target to affect such host-parasite interaction to aid parasite killing.
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| Date |
2010
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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/379/1/Thesis_Arunima.pdf
Biswas, Arunima (2010) Host-Parasite Interaction: Modulation of Signaling Pathways in Macrophage and Leishmania and its Impact on Parasite Infectivity. PhD thesis, Jadavpur University. |
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| Relation |
http://www.eprints.iicb.res.in/379/
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