Fig. 8

Model for the transmigration, adhesion and invasion by C. jejuni during infection of polarized Caco-2 cells depends on the expression of HtrA and tight junction protein occludin. a Upon infection of Caco-2 wild-type cells, C. jejuni exploits the secreted serine protease HtrA to cleave the apical tight junction protein occludin (this work) and the adherens junction protein E-cadherin [11]. Cleavage of both factors weakens the tight and adherens junctions, respectively, followed by entering of wild-type C. jejuni into the intercellular space between neighboring cells of the gut epithelium and paracellular transmigration. This enables the bacteria to reach basal surfaces and the fibronectin-integrin complex that connect the cells with underlying tissue. This complex is used as the receptor for the C. jejuni adhesins CadF/FlpA to bind and enter the epithelial cells from the bottom. As cleavage of the junctional proteins by HtrA is required for this outcome, ∆htrA mutant bacteria are strongly diminished in transmigration, adhesion and invasion of polarized Caco-2 cells. b During infection of Caco-2 cells with occludin knockout, the tight junctions are slightly weaker compared to wild-type cells as confirmed by TER measurement and immunofluorescence microscopy. This leads to enhanced transmigration, adhesion and invasion rates by wild-type C. jejuni. In addition, absence of occludin even allows ∆htrA bacteria to transmigrate to some extent, resulting in increased cell binding and invasion, albeit still at lower rates compared to wild-type C. jejuni