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

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • University of California at Irvine

Details

Original languageEnglish (US)
Pages (from-to)24796-24807
Number of pages12
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number49
StatusPublished - Dec 3 2019
Peer-reviewedYes

Abstract

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 of monocytes in the brain during T. gondii CNS infection.

    Research areas

  • Blood–brain barrier, CNS infection, LPS, Monocyte, Toxoplasma gondii

Citation formats

APA

Schneider, C. A., Figueroa Velez, D. X., Azevedo, R., Hoover, E. M., Tran, C. J., Lo, C., ... Lodoen, M. B. (2019). Imaging the dynamic recruitment of monocytes to the blood–brain barrier and specific brain regions during Toxoplasma gondii infection. Proceedings of the National Academy of Sciences of the United States of America, 116(49), 24796-24807. https://doi.org/10.1073/pnas.1915778116

Harvard

Schneider, CA, Figueroa Velez, DX, Azevedo, R, Hoover, EM, Tran, CJ, Lo, C, Vadpey, O, Gandhi, SP & Lodoen, MB 2019, 'Imaging the dynamic recruitment of monocytes to the blood–brain barrier and specific brain regions during Toxoplasma gondii infection', Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 49, pp. 24796-24807. https://doi.org/10.1073/pnas.1915778116