Cerebral complement C1q activation in chronic Toxoplasma infection.
Exposure to the neurotropic parasite, Toxoplasma gondii, causes significant brain and behavioral anomalies in humans and other mammals. Understanding the cellular mechanisms of T. gondii-generated brain pathologies would aid the advancement of novel strategies to reduce disease. Complement factor C1q is part of a classic immune pathway that functions peripherally to tag and remove infectious agents and cellular debris from circulation. In the developing and adult brain, C1q modifies neuronal architecture through synapse marking and pruning. T. gondii exposure and complement activation have both been implicated in the development of complex brain disorders such as schizophrenia. Thus, it seems logical that mechanistically, the physiological pathways associated with these two factors are connected. We employed a rodent model of chronic infection to investigate the extent to which cyst presence in the brain triggers activation of cerebral C1q. Compared to uninfected mice, cortical C1q was highly expressed at both the RNA and protein levels in infected animals bearing a high cyst burden. In these mice, C1q protein localized to cytoplasm, adjacent to GFAP-labeled astrocytes, near degenerating cysts, and in punctate patterns along processes. In summary, our results demonstrated an upregulation of cerebral C1q in response to latent T. gondii infection. Our data preliminarily suggest that this complement activity may aid in the clearance of this parasite from the CNS and in so doing, have consequences for the connectivity of neighboring cells and synapses.
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 1105, Baltimore, MD 21287-4933, USA.
Jianchun
J
Xiao
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 1105, Baltimore, MD 21287-4933, USA.
Ye
Y
Li
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 1105, Baltimore, MD 21287-4933, USA.
Kristin L
KL
Gressitt
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 1105, Baltimore, MD 21287-4933, USA.
Helen
H
He
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
Geetha
G
Kannan
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
Tracey L
TL
Schultz
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
Nadezhda
N
Svezhova
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
Vern B
VB
Carruthers
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Mikhail V
MV
Pletnikov
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 1105, Baltimore, MD 21287-4933, USA.
Robert H
RH
Yolken
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 1105, Baltimore, MD 21287-4933, USA. Electronic address: eseverance@jhmi.edu.
Emily G
EG
Severance
D000818:Animals; D002540:Cerebral Cortex / Q000276:immunology* / Q000469:parasitology*; D002908:Chronic Disease; D015922:Complement C1q / Q000378:metabolism*; D003560:Cysts / Q000276:immunology; D005260:Female; D051379:Mice; D014123:Toxoplasmosis / Q000276:immunology*
D015922:Complement C1q
Glia; MAG1 antibodies; Neurons; Prefrontal cortex; Psychiatry; Toxoplasmosis