Investigation of the effects of Campylobacter jejuni virulence factors in human cells: different pathways involved

The gram-negative bacterium Campylobacter jejuni represents a major agent causing food-borne gastroenteritis in humans worldwide. Many bacterial pathogens, including C. jejuni, utilize outer membrane vesicles (OMVs) to transport virulence factors, such as the CDT (cytolethal distending toxin), into host cells. To date, different authors described the peculiar relationship among C. jejuni virulence factors and human intestinal and myeloid cells. The aim of this work was to investigate the effects of C. jejuni virulence factors in human cells focusing the attention on cellular pathways that this bacterium activates or deactivates during host cell infection. Among the several virulence factors, the CDT was the most investigated. To do that, effects induced by three different C. jejuni wild type strains were compared with the effects induced by two C. jejuni cdt mutant strains, C. jejuni cdtA and cdtB mutant strains, in three different cell lines: monocytes isolated from donor’s human blood, tumour myeloid cells (U937) and human intestinal epithelial cells (T84). C. jejuni lysates, OMVs and whole cells were separately used for the infections. Carried out cytometric, microscopy and molecular analyses revealed that C. jejuni induce DNA damage, apoptosis, mitochondrial and lysosomal destabilization as well as intracellular lipid content alterations, ICAM-1 upregulation and activation of autophagic, secretory and endocytic pathways in a CDT dependent manner. Nevertheless, although they are important for C. jejuni infection, CDT seems not to have a role in ER stress and UPR activation, CD14 and CD59 upregulation. Involvement of all these pathways enhances C. jejuni invasion, persistence and survival, allowing the possible onset of post infectious sequelae such as the Guillain-Barré syndrome.