CHARACTERIZING THE CNS IMMUNE RESPONSE PROVOKED BY TWO GENETICALLY DIVERGENT STRAINS OF TOXOPLASMA GONDII

Persistent Link:
http://hdl.handle.net/10150/612979
Title:
CHARACTERIZING THE CNS IMMUNE RESPONSE PROVOKED BY TWO GENETICALLY DIVERGENT STRAINS OF TOXOPLASMA GONDII
Author:
GHOTMI, YARAH
Issue Date:
2016
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Toxoplasma gondii is an obligate intracellular parasite that infects a wide range of intermediate hosts, including humans and rodents. For both humans and rodents, once infected Toxoplasma establishes a lifelong infection in the central nervous system (CNS). In humans, this tropism for the brain underlies Toxoplasma’s ability to cause a wide range of neurological consequences in the immunocompromised, in the developing fetus and occasionally in immunocompetent individuals. The outcomes of symptomatic Toxoplasma infection can range from vision-affecting chorioretinitis to encephalitis to death. Recent human data suggest that the genotype of the infecting Toxoplasma strain may influence disease severity; however, how these strains differ in their ability to cause disease is not well understood. Previous in vitro and acute infection studies in mice have shown that strain-specific polymorphic effector proteins that are secreted and injected into host cells can differentially modulate signaling pathways, affecting cellular functions such as cytokine production. It is unknown if these differences or others lead to strainspecific CNS immune responses. To address this gap in knowledge, we used the mouse model of toxoplasmosis to characterize the neuroinflammatory response generated by two genetically divergent Toxoplasma strains (type II and type III). Using immunohistochemistry and an unbiased stereotyped computer program, Simple PCI, we quantified T cell and macrophage responses in the CNS. We also performed a 25-plex cytokine assay to characterize the CNS cytokine milieu in mice infected with either type II or type III parasites. Remarkably, despite having similar parasite burdens at 3 weeks post infection, we found that type III infection causes a significantly higher number of infiltrating T cells and macrophages/microglia and elicits a more robust pro-inflammatory cytokine milieu compared to type II infection. On-going work is focused on creating transgenic Toxoplasma strains that will enable us to dissect out the role of known effector proteins in these strain-specific neuroinflammatory responses.
Type:
text; Electronic Thesis
Degree Name:
B.S.
Degree Level:
Bachelors
Degree Program:
Honors College; Neuroscience and Cognitive Science
Degree Grantor:
University of Arizona
Advisor:
Koshy, Anita

Full metadata record

DC FieldValue Language
dc.language.isoen_USen
dc.titleCHARACTERIZING THE CNS IMMUNE RESPONSE PROVOKED BY TWO GENETICALLY DIVERGENT STRAINS OF TOXOPLASMA GONDIIen_US
dc.creatorGHOTMI, YARAHen
dc.contributor.authorGHOTMI, YARAHen
dc.date.issued2016-
dc.publisherThe University of Arizona.en
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en
dc.description.abstractToxoplasma gondii is an obligate intracellular parasite that infects a wide range of intermediate hosts, including humans and rodents. For both humans and rodents, once infected Toxoplasma establishes a lifelong infection in the central nervous system (CNS). In humans, this tropism for the brain underlies Toxoplasma’s ability to cause a wide range of neurological consequences in the immunocompromised, in the developing fetus and occasionally in immunocompetent individuals. The outcomes of symptomatic Toxoplasma infection can range from vision-affecting chorioretinitis to encephalitis to death. Recent human data suggest that the genotype of the infecting Toxoplasma strain may influence disease severity; however, how these strains differ in their ability to cause disease is not well understood. Previous in vitro and acute infection studies in mice have shown that strain-specific polymorphic effector proteins that are secreted and injected into host cells can differentially modulate signaling pathways, affecting cellular functions such as cytokine production. It is unknown if these differences or others lead to strainspecific CNS immune responses. To address this gap in knowledge, we used the mouse model of toxoplasmosis to characterize the neuroinflammatory response generated by two genetically divergent Toxoplasma strains (type II and type III). Using immunohistochemistry and an unbiased stereotyped computer program, Simple PCI, we quantified T cell and macrophage responses in the CNS. We also performed a 25-plex cytokine assay to characterize the CNS cytokine milieu in mice infected with either type II or type III parasites. Remarkably, despite having similar parasite burdens at 3 weeks post infection, we found that type III infection causes a significantly higher number of infiltrating T cells and macrophages/microglia and elicits a more robust pro-inflammatory cytokine milieu compared to type II infection. On-going work is focused on creating transgenic Toxoplasma strains that will enable us to dissect out the role of known effector proteins in these strain-specific neuroinflammatory responses.en
dc.typetexten
dc.typeElectronic Thesisen
thesis.degree.nameB.S.en
thesis.degree.levelBachelorsen
thesis.degree.disciplineHonors Collegeen
thesis.degree.disciplineNeuroscience and Cognitive Scienceen
thesis.degree.grantorUniversity of Arizonaen
dc.contributor.advisorKoshy, Anitaen
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