Intracellular transport of Toxoplasma gondii through the blood–brain barrier

Abstract Toxoplasma gondii establishes latent infection in the central nervous system of immunocompentent hosts. Toxoplasmic encephalitis is a life threatening reactivation of latent infection in the brain of immunocompromised patients. To further understand the mechanisms of entry into the brain of...

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Bibliographic Details
Published in:	Journal of neuroimmunology Vol. 232; no. 1; pp. 119 - 130
Main Authors:	Lachenmaier, Sabrina M, Deli, Mária A, Meissner, Markus, Liesenfeld, Oliver
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 01-03-2011
Subjects:	Allergy and Immunology Animals Antigen-Presenting Cells - metabolism Antigen-Presenting Cells - microbiology Blood-Brain Barrier - immunology Blood-Brain Barrier - metabolism Blood–brain barrier CD11c Antigen - biosynthesis Cell Separation Cells, Cultured Chemotaxis, Leukocyte - immunology Coculture Techniques Endothelial Cells - immunology Endothelial Cells - metabolism Endothelial Cells - microbiology Flow Cytometry Gene Expression Gene Expression Profiling In Situ Hybridization Intercellular Adhesion Molecule-1 - biosynthesis Lymphocytes - metabolism Lymphocytes - microbiology Mice Microscopy, Fluorescence Neuroinvasion Neurology Polymerase Chain Reaction Rats Rats, Wistar Toxoplasma - immunology Toxoplasma - pathogenicity Toxoplasma gondii Toxoplasmosis, Cerebral - immunology Toxoplasmosis, Cerebral - metabolism Transendothelial migration Neuroinvasion Toxoplasma gondii Transendothelial migration Blood–brain barrier
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Summary:	Abstract Toxoplasma gondii establishes latent infection in the central nervous system of immunocompentent hosts. Toxoplasmic encephalitis is a life threatening reactivation of latent infection in the brain of immunocompromised patients. To further understand the mechanisms of entry into the brain of T. gondii we investigated host molecules and cells involved in the passage of the parasite through the blood–brain barrier. First, using microarrays brain endothelial cells were found to upregulate, among others, chemokines and adhesion molecules following infection with tachyzoites. Using flow cytometry we observed upregulated ICAM-1 expression on the surface of brain endothelial cells following infection; ICAM-1 expression was further increased after pre-incubation with IFN-γ. Compared to RH tachyzoites, ME49 tachyzoites induced a stronger upregulation of ICAM-1 and an earlier and stronger IL-6 and MCP-1 secretion by brain endothelial cells. Using an in vitro coculture model of the BBB (primary glia cells and brain endothelial cells) we found a stronger migration of infected antigen-presenting cells compared to lymphocytes (4.63% vs. 0.6% of all cells) across the BBB. Among all antigen-presenting cells CD11b+ /CD11c+ cells showed the highest infection rate, whereas the majority of infected cells that migrated through the blood–brain barrier were CD11b+ /CD11c− cells. Infection of PBMCs with type I or type II Toxoplasma strains resulted in similar patterns of cell migration across the in vitro BBB model. In conclusion, these results suggest that T. gondii modulates gene expression of brain endothelial cells to promote its own migration through the blood–brain barrier in a ‘Trojan horse’ manner. Cells expressing CD11b either with or without CD11c are likely candidate cells for the intracellular transport of T. gondii across the BBB. T. gondii type I and type II strains induced similar migration patterns of antigen-presenting cells across the in vitro BBB.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0165-5728 1872-8421
DOI:	10.1016/j.jneuroim.2010.10.029