Toxoplasma gondii excreted/secreted proteases disrupt intercellular junction proteins in epithelial cell monolayers to facilitate tachyzoites paracellular migration

• DOI: 10.1111/cmi.13283
• Publication Date: 2020-10-27T18:52:11Z
• Authors: Carlos J. Ramírez...; Rosalba Cruz‐Mirón; Noé Lagunas‐Cortés; Mónica Mondragón‐...; Ricardo Mondragon...; Sirenia González‐...; Ricardo Mondragón...
• Keywords: Paracellular transport; Occludin; Claudin

Toxoplasma gondii shows high dissemination and migration properties across biological barriers infecting immunologically privileged organs. uses different routes for dissemination; however, the mechanisms are not fully understood. Herein, we studied effects of proteases present in excretion/secretion products (ESPs) on MDCK cell monolayers. Ultrastructural analysis showed that ESPs disrupt intercellular junctions (IJ) adjacent cells. The tight junction (TJ) proteins ZO-1, occludin, claudin-1 suffered a progressive decrease protein levels upon treatment. In addition, induced mislocalization such TJ proteins, along with adherent E-cadherin, this was prevented by pre-treating protease inhibitors. Reorganisation cytoskeleton also observed. Endocytosis inhibitors, Dyngo®-4a Dynasore, impeded modifications, suggesting internalisation is triggered hence contributing to loss IJ. observed disruption went line transepithelial electrical resistance monolayers, which significantly blocked metalloprotease serine Moreover, exposure monolayers facilitated paracellular tachyzoites. Our results demonstrate contain can IJ epithelial could facilitate route tissue migration.