Biology ETDs
The role of Toxoplasma gondii dense granule protein GRA24 in signaling and immunity during infection
Publication Date
Summer 7-14-2021
Abstract
Toxoplasma gondii is a pathogen whose control partly depends upon Toll-like receptors (TLR) 11 and 12, that signal through MyD88. Yet, human TLR11 and TLR12 are nonfunctional, motivating us to investigate MyD88-independent immune pathways. Parasite dense granule protein GRA24 activates p38 MAPK independently of MyD88 in macrophages. Using wild-type and GRA24-deleted T. gondii strains, I demonstrate GRA24 activates p38 MAPK, resulting in IL-12 production, and protective immunity. Furthermore, GRA24 triggers p38 MAPK-dependent CX3CL1 production. GRA24 also induces CCL17 and Ppbp independently of p38 MAPK. Additionally, I demonstrate GRA24 downregulates CCL12. Furthermore, IL-15 is negatively regulated by GRA24 through activation of p38 MAPK activation. Moreover, I show GRA24 may play a role in CD4+ T cell recruitment during T. gondii infection. Together, this research is a prime example of the fine balance of inflammatory events triggered by T. gondii to ensure persistence of both host and parasite.
Language
English
Keywords
Toxoplasma gondii, Myd88, GRA24, dense granule protein
Document Type
Dissertation
Degree Name
Biology
Level of Degree
Doctoral
Department Name
UNM Biology Department
First Committee Member (Chair)
Dr. Eric Y. Denkers
Second Committee Member
Dr. Irene Salinas
Third Committee Member
Dr. Eric S. Loker
Fourth Committee Member
Dr. David J. Bzik
Recommended Citation
Mercer, Heather L.. "The role of Toxoplasma gondii dense granule protein GRA24 in signaling and immunity during infection." (2021). https://digitalrepository.unm.edu/biol_etds/385