The secreted kinase ROP17 promotes Toxoplasma gondii dissemination by hijacking monocyte tissue migration

Lisa L. Drewry, Nathaniel G. Jones, Quiling Wang, Michael D. Onken, Mark J. Miller, L. David Sibley

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The protozoan parasite Toxoplasma gondii is thought to exploit monocyte trafficking to facilitate dissemination across endothelial barriers such as the blood–brain barrier. Here, we analysed the migration of parasitized monocytes in model endothelial and interstitial environments. We report that infection enhanced monocyte locomotion on the surface of endothelial cells, but profoundly inhibited monocyte transmigration across endothelial barriers. By contrast, infection robustly increased monocyte and macrophage migration through collagen-rich tissues in a Rho–ROCK-dependent manner consistent with integrin-independent interstitial migration. We further demonstrated that the secreted T. gondii protein kinase ROP17 was required for enhanced tissue migration. In vivo, ROP17-deficient parasites failed to upregulate monocyte tissue migration and exhibited an early dissemination delay, leading to prolonged mouse survival. Our findings indicate that the parasite-induced changes in monocyte motility primarily facilitate the transport of T. gondii through tissues and promote systemic dissemination, rather than shuttle parasites across the blood–brain barrier via extravasation.

Original languageEnglish
Pages (from-to)1951-1963
Number of pages13
JournalNature microbiology
Volume4
Issue number11
DOIs
StatePublished - Nov 1 2019

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