Studies to elucidate host immune mechanisms involved in the blastocystis sp. subtype 3 symptomatic and asymptomatic infection / Sheela Devi Sugadan
Blastocystis sp. is an enteric protozoan parasite of humans and many animals. Blastocystis sp. ST3 proves to be the highest frequency case in most populations around the world and it is further distinguished into symptomatic and asymptomatic isolates based on the clinical symptoms exhibited by...
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| Format: | Thesis |
| Published: |
2019
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| Online Access: | http://studentsrepo.um.edu.my/13252/4/sheela.pdf http://studentsrepo.um.edu.my/13252/ |
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| Summary: | Blastocystis sp. is an enteric protozoan parasite of humans and many animals.
Blastocystis sp. ST3 proves to be the highest frequency case in most populations around
the world and it is further distinguished into symptomatic and asymptomatic isolates
based on the clinical symptoms exhibited by infected individuals. Phenotypic and
genotypic studies implicate the distinctiveness of this parasite. However, the pathogenesis
of this parasite is still in a grey area. Therefore, this study was aimed to analyse the
immunopathogenesis of Blastocystis sp. ST3 symptomatic and asymptomatic isolates.
The immunopathogenesis of this parasite was analysed by assessing the (1) characteristic
of antigen immune response (antigen specificity and diversity) and (2) the modulations
of innate and adaptive immune responses. The antigen specificity was evaluated by
immunising Balb/c mice with 20µg/ml solubilised antigen. Results has shown pre?dominant of Th1 (IFN? and IL-2) cytokine response and IgG2a antibody response
induced by symptomatic antigen immunised group and pre-dominant of Th2 (IL-4 and
IL-10) cytokine response and IgG1 antibody response induced by asymptomatic antigen
immunised group which has shown diverse specific immune response. Antigen diversity
analysis was performed by co-culturing sera (10-fold dilution) obtained from mice
immunised with Blastocystis sp. symptomatic and asymptomatic antigens and the
respective Blastocystis sp. live cells through complement dependant cell cytotoxicity
(CDC) assay. The sera (at 101
concentrations) from symptomatic and asymptomatic
antigen immunised mice were able to specifically lyse the respective live cells with an
average percentage of 82% and 86% respectively. There was almost 50% cross-reactivity
iv
observed between Blastocystis sp. ST3 isolates origin from the same group which proving
high antigen diversity. However, there was only 17% cross-reactivity observed between
the sera and cells of different group (symptomatic and asymptomatic isolates). Further in
vitro studies were carried out to investigate the immune modulation triggered by
Blastocystis sp. antigens towards antigen presenting cells (macrophages and monocytes).
Blastocystis sp. induced apoptosis in macrophages as early as 6 hours of incubation while
monocytes suppressed the secretions of pro-inflammatory cytokines through increased
expressions of PD-1 during short- and long-term antigen-exposure resembling acute and
chronic infection respectively. This observation implicates the immunosuppressive
features of Blastocystis sp. which could be utilised to evade host innate defence
mechanisms. Next, the effect of Blastocystis sp. antigen on T cell immune modulation
(adaptive immunity) was assessed by introducing symptomatic and asymptomatic
parasite antigens to the blood mononuclear cells (PBMCs) in vitro. The antigens resulted
in elevated levels of T cell co-inhibitory molecules and reduced functional T cell pro?inflammatory cytokines (IL-2 and IFN?) suggesting that the parasite is able to cause T
cell �exhaustion� or dysfunction by symptomatic and asymptomatic antigens at 83% and
94% respectively. This study underscores the importance of identifying the differences of
immune responses and immunomodulation mechanisms induced by Blastocystis sp. ST3
symptomatic and asymptomatic isolates in a host. The study for the first time, had shed
light on the distinct host immune response induced by Blastocystis sp. ST3 symptomatic
and asymptomatic isolates implicating that these isolates could portrayed different
immunopathogenesis in the host intestine.
Keywords: Blastocystis sp., symptomatic, asymptomatic, Subtype 3,
Immunopathogenesis.
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