Stockholm university
Department of Molecular Biosciences, The Wenner-Gren Institute

Toxoplasma traps immune cells in blood vessels to rapidly colonize the brain

A recent study published in Nature Communications by the Barragan group reveals how Toxoplasma manipulates infected leukocytes, causing them to become sequestered in cerebral capillaries. After replicating, the parasites exit the leukocytes and swiftly reach neurons. These findings provide new insight into the parasite's journey from the bloodstream into the brain.

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 novel mechanism for T. gondii's rapid access to cortical neurons during primary infection.

Photo: Matias Rodriguez
The image shows how Toxoplasma gondii parasites (green) invade brain tissue through a multi-step process. Photo: Matias Rodriguez 

 

Read the full study in Nature.

Read the article published in DN about the study (In Swedish)

Research subject
Infection and Immunobiology
Research group
Group Barragan

Our current research on the pathobiology of parasitic infections integrates molecular parasitology with immunology and cell biology to understand how obligate intracellular parasites interact with the host.

Antonio Barragan
Read more about

Last updated: April 16, 2025

Source: MBW

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