Imaging the dynamic recruitment of monocytes to the blood–brain barrier and specific brain regions during Toxoplasma gondii infection

Brain infection by the parasite Toxoplasma gondii in mice is thought to generate vulnerability to predation by mechanisms that remain elusive. Monocytes play a key role in host defense and inflammation and are critical for controlling T. gondii. However, the dynamic and regional relationship between...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2019-12, Vol.116 (49), p.24796-24807
Main Authors: Schneider, Christine A., Velez, Dario X. Figueroa, Azevedo, Ricardo, Hoover, Evelyn M., Tran, Cuong J., Lo, Chelsie, Vadpey, Omid, Gandhi, Sunil P., Lodoen, Melissa B.
Format: Article
Language:English
Subjects:
Animals
Antigens, Ly - metabolism
Biological Sciences
Blood vessels
Blood-brain barrier
Blood-Brain Barrier - diagnostic imaging
Blood-Brain Barrier - metabolism
Brain
Brain - diagnostic imaging
Brain - metabolism
CCR2 protein
Clusters
Computational neuroscience
CX3C Chemokine Receptor 1 - metabolism
CX3CR1 protein
Disease Models, Animal
Female
Image segmentation
Infections
Inflammation
Lipopolysaccharides
Localization
Male
Mice
Mice, Inbred C57BL
Monocyte chemoattractant protein 1
Monocytes
Monocytes - metabolism
Neuroimaging
Olfactory bulb
Parasites
Parenchyma
Predation
Protozoa
Receptors, CCR2 - metabolism
Recruitment
Rodents
Toxoplasma gondii
Toxoplasmosis - diagnostic imaging
Toxoplasmosis - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Brain infection by the parasite Toxoplasma gondii in mice is thought to generate vulnerability to predation by mechanisms that remain elusive. Monocytes play a key role in host defense and inflammation and are critical for controlling T. gondii. However, the dynamic and regional relationship between brain-infiltrating monocytes and parasites is unknown. We report the mobilization of inflammatory (CCR2+Ly6Chi) and patrolling (CX3CR1+Ly6Clo) monocytes into the blood and brain during T. gondii infection of C57BL/6J and CCR2RFP/+CX3CR1GFP/+ mice. Longitudinal analysis of mice using 2-photon intravital imaging of the brain through cranial windows revealed that CCR2-RFP monocytes were recruited to the blood–brain barrier (BBB) within 2 wk of T. gondii infection, exhibited distinct rolling and crawling behavior, and accumulated within the vessel lumen before entering the parenchyma. Optical clearing of intact T. gondii-infected brains using iDISCO+ and light-sheet microscopy enabled global 3D detection of monocytes. Clusters of T. gondii and individual monocytes across the brain were identified using an automated cell segmentation pipeline, and monocytes were found to be significantly correlated with sites of T. gondii clusters. Computational alignment of brains to the Allen annotated reference atlas [E. S. Lein et al., Nature 445:168–176 (2007)] indicated a consistent pattern of monocyte infiltration during T. gondii infection to the olfactory tubercle, in contrast to LPS treatment of mice, which resulted in a diffuse distribution of monocytes across multiple brain regions. These data provide insights into the dynamics of monocyte recruitment to the BBB and the highly regionalized localization ofmonocytes in the brain during T. gondii CNS infection.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1915778116