ICAM-1/CD18-mediated sequestration of parasitized phagocytes in cortical capillaries promotes neuronal colonization by Toxoplasma gondii

Matias E. Rodriguez, Ali Hassan, Nikolaos Linaroudis, Felix Harryson-Oliveberg, Arne L. Hoeve and Antonio Barragan ()
Additional contact information
Matias E. Rodriguez: Stockholm University
Ali Hassan: Stockholm University
Nikolaos Linaroudis: Stockholm University
Felix Harryson-Oliveberg: Stockholm University
Arne L. Hoeve: Stockholm University
Antonio Barragan: Stockholm University

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Microbial translocation across the blood-brain barrier (BBB) is a prerequisite for colonization of the central nervous system. The obligate intracellular parasite Toxoplasma gondii chronically infects the brain parenchyma of humans and animals, in a remarkably stealthy fashion. We investigated the mechanisms of BBB traversal by T. gondii (genotypes I, II, III) and T. gondii-infected leukocytes, using intracarotid arterial delivery into the cerebral circulation of mice. Unexpectedly, parasitized dendritic cells (DCs) and other peripheral blood mononuclear cells were found to persistently sequester within cortical capillaries. Post-replicative egress of T. gondii from sequestered DCs was followed by rapid parasite localization within cortical neurons. Infection-induced microvascular inflammation dramatically elevated the sequestration of parasitized DCs, while treatments targeting the ICAM-1/CD18 leukocyte adhesion axis with blocking antibodies strongly reverted sequestration. The parasite effectors TgWIP and GRA15, known to promote leukocyte hypermigration and inflammatory activation, further increased both the capillary sequestration of infected DCs and cerebral parasite loads in a strain-dependent manner. These findings reveal that the sequestration of parasitized leukocytes in cortical capillaries, with subsequent BBB traversal following parasite egress, provides a mechanism for T. gondii’s rapid access to cortical neurons during primary infection.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-58655-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58655-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-58655-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().