JlpA of Campylobacter jejuni interacts with surface-exposed heat shock protein 90α and triggers signalling pathways leading to the activation of NF-κB and p38 MAP kinase in epithelial cells

Campylobacter jejuni is a leading cause of acute bacterial gastroenteritis in humans. The mechanism by which C. jejuni interacts with host cells, however, is still poorly understood. Our previous study has shown that the C. jejuni surface lipoprotein JlpA mediates adherence of the bacterium to epithelial cells. In this report, we demonstrated that JlpA interacts with HEp-2 cell surface heat shock protein (Hsp) 90alpha and initiates signalling pathways leading to activation of NF-kappaB and p38 MAP kinase. Gel overlay and GST pull down assays showed that JlpA interacts with Hsp90alpha. Geldanamycin, a specific inhibitor of Hsp90, and anti-human Hsp90alpha antibody significantly blocked the interaction between JlpA and Hsp90alpha, suggesting a direct interaction between JlpA and HEp-2 cell surface-exposed Hsp90alpha. The treatment of HEp-2 cells with GST-JlpA initiated two signalling pathways: one leading to the phosphorylation and degradation of IkappaB and nuclear translocation of NF-kappaB; and another one to the phosphorylation of p38 MAP kinase. The activation of NF-kappaB and p38 MAP kinase in HEp-2 cells suggest that JlpA triggers inflammatory/immune responses in host cells following C. jejuni infection.