TY - JOUR
T1 - Epigenetic dysregulation of host gene expression in Toxoplasma infection with specific reference to dopamine and amyloid pathways
AU - Syn, Genevieve
AU - Anderson, Denise
AU - Blackwell, Jenefer M.
AU - Jamieson, Sarra E.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - Recent interest has focussed on the influence of infectious disease organisms on the host epigenome. Toxoplasma gondii infection acquired congenitally or in early life is associated with severe ocular and brain developmental anomalies, while persistent asymptomatic infection is a proposed risk factor for neurodegenerative and psychiatric disorders, including Parkinson's and Alzheimer's Diseases, and schizophrenia. Genome-wide analysis of the host methylome and transcriptome following T. gondii infection in a retinal cell line identified genes (132, 186 and 128 genes at 2, 6 and 24 h post-infection) concordant for methylation and expression, i.e. hypermethylated and decreased expression or hypomethylated and increased expression. Pathway analyses showed perturbation of two neurologically-associated pathways: dopamine-DARPP32 feedback in cAMP signalling (p-value = 8.3 × 10−5; adjusted p-value = 0.020); and amyloid processing (p-value = 1.0 × 10−3; adjusted p-value = 0.043). Amyloid Precursor Protein (APP) decreased in level following T. gondii infection. These results are of interest given the expression of APP early in nervous system development affecting neural migration and the role of amyloid processing in Alzheimer's disease, while dopamine has roles in the developing retina as well as in Parkinson's disease and schizophrenia. Our results provide a possible functional link between T. gondii infection and congenital/early life and adult neurological clinical signs.
AB - Recent interest has focussed on the influence of infectious disease organisms on the host epigenome. Toxoplasma gondii infection acquired congenitally or in early life is associated with severe ocular and brain developmental anomalies, while persistent asymptomatic infection is a proposed risk factor for neurodegenerative and psychiatric disorders, including Parkinson's and Alzheimer's Diseases, and schizophrenia. Genome-wide analysis of the host methylome and transcriptome following T. gondii infection in a retinal cell line identified genes (132, 186 and 128 genes at 2, 6 and 24 h post-infection) concordant for methylation and expression, i.e. hypermethylated and decreased expression or hypomethylated and increased expression. Pathway analyses showed perturbation of two neurologically-associated pathways: dopamine-DARPP32 feedback in cAMP signalling (p-value = 8.3 × 10−5; adjusted p-value = 0.020); and amyloid processing (p-value = 1.0 × 10−3; adjusted p-value = 0.043). Amyloid Precursor Protein (APP) decreased in level following T. gondii infection. These results are of interest given the expression of APP early in nervous system development affecting neural migration and the role of amyloid processing in Alzheimer's disease, while dopamine has roles in the developing retina as well as in Parkinson's disease and schizophrenia. Our results provide a possible functional link between T. gondii infection and congenital/early life and adult neurological clinical signs.
KW - 450 K methylation array
KW - Alzheimer's disease
KW - Amyloid
KW - Dopamine
KW - HT-12 v4 expression array
KW - Parkinson's disease
KW - Schizophrenia
KW - Toxoplasma
UR - http://www.scopus.com/inward/record.url?scp=85050629810&partnerID=8YFLogxK
U2 - 10.1016/j.meegid.2018.07.034
DO - 10.1016/j.meegid.2018.07.034
M3 - Article
C2 - 30055328
AN - SCOPUS:85050629810
SN - 1567-1348
VL - 65
SP - 159
EP - 162
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
ER -
