Real-time imaging of Toxoplasma-infected human monocytes under fluidic shear stress reveals rapid translocation of intracellular parasites across endothelial barriers.

Autor: Ueno N; Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, CA, USA., Harker KS, Clarke EV, McWhorter FY, Liu WF, Tenner AJ, Lodoen MB
Jazyk: angličtina
Zdroj: Cellular microbiology [Cell Microbiol] 2014 Apr; Vol. 16 (4), pp. 580-95. Date of Electronic Publication: 2013 Dec 04.
DOI: 10.1111/cmi.12239
Abstrakt: Peripheral blood monocytes are actively infected by Toxoplasma gondii and can function as 'Trojan horses' for parasite spread in the bloodstream. Using dynamic live-cell imaging, we visualized the transendothelial migration (TEM) of T. gondii-infected primary human monocytes during the initial minutes following contact with human endothelium. On average, infected and uninfected monocytes required only 9.8 and 4.1 min, respectively, to complete TEM. Infection increased monocyte crawling distances and velocities on endothelium, but overall TEM frequencies were comparable between infected and uninfected cells. In the vasculature, monocytes adhere to endothelium under the conditions of shear stress found in rapidly flowing blood. Remarkably, the addition of fluidic shear stress increased the TEM frequency of infected monocytes 4.5-fold compared to static conditions (to 45.2% from 10.3%). Infection led to a modest increase in expression of the high-affinityconformation of the monocyte integrin Mac-1 (CD11b/CD18), and Mac-1 accumulated near endothelial junctions during TEM. Blocking Mac-1 inhibited the crawling and TEM of infected monocytes to a greater degree than uninfected monocytes, and blocking the Mac-1 ligand, ICAM-1, dramatically reduced crawling and TEM for both populations. These findings contribute to a greater understanding of parasite dissemination from the vasculature into tissues.
(© 2013 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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