Identification of toxoplasma gondii genes involved in the strain-specific modulation of IL-12 cytokine secretion

Toxoplasma gondii is an intracellular pathogen that causes life-threatening toxoplasmosis in developing fetuses and immune-compromised individuals. An immune response to a Toxoplasma infection is characterized by the stimulation of high levels of interleukin- 12 (IL- 12), followed by the production of interferon-y (IFN-y) by immune cells. Although IFN-y is the main mediator of resistance to Toxoplasma infection, Toxoplasma is able to manipulate the immune response through the regulation of IL- 12 production. Toxoplasma has been shown to modulate the induction of IL-12 in a strain-specific manner. An infection with a type II strain, but not type I and III strains, induce high levels of IL- 12 production by macrophages in vitro. Previous studies have implicated two Toxoplasma genes that play a role in this strainspecific difference in IL- 12 production. A rhoptry protein kinase, ROP 16, from type I and III strains, was found to be crucial in the suppression of IL-12. A type II dense granule protein, GRA 15, induces IL-12 through NF-KB activation. I have screened F1 progeny from a type III x type II cross for IL-12 induction and NF-KB activation. My preliminary experiments indicate that there are other Toxoplasma factors involved in the strain-specific inhibition of IL-12, and this inhibition has a genetic basis. To understand the role of IL-12 regulation by Toxoplasma, I intend to (i) identify novel Toxoplasma genes involved in the inhibition of IL- 12 secretion (ii) test and characterize the effects of the Toxoplasma protein ROP38 on IL-12 signaling and (iii) determine the target/s of Toxoplasma inhibition of IL-12 production.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2011

Author dc:creator

• Mc Kell, Renée Abba

Advisor dc:contributor.advisor

• Jeroen Saeij.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/65751

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/65751