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Problem Statement Campylobacter jejuni adheres, invades and resides within intestinal epithelial cells (IECs). However, the exact process at the cellular level leading to diarrhoeal disease is poorly understood. There have been studies that link intestinal inflammation and the unfolded protein response (UPR), which is a conserved pathway to restore homeostasis in the endoplasmic reticulum. Recent data has shown that C. jejuni activates UPR through IRE1α pathway. Here, we investigated the activation of the UPR through PERK, IRE1α, and ATF6 pathways by C. jejuni. Approach To investigate whether C. jejuni infection induces UPR in IECs, T84 cells were infected with C. jejuni 11168H, 81-176, and 488 wild-type strains with different exposure times. RNA and proteins were isolated from infected cells, and the induction of UPR by C. jejuni wild-type strains was observed using transcription and proteomic methods. Results The activation of all three UPR branches, PERK, IRE1α, and ATF6 was demonstrated by increased levels of transcription of chop, spliced xbp1, and atf6, respectively compared to uninfected control. The upregulation of these genes was confirmed by western blot, which showed increased amount of proteins for CHOP, phosphorylated eIF2α, and spliced XBP1 compared to the control. Conclusions The combined results demonstrate that C. jejuni induces the UPR through all three pathways. This study opens the way forward for improved understanding of the interaction between C. jejuni and IECs via UPR activation leading to intestinal inflammation. This understanding will further benefit the investigation of cellular pathways triggered by C. jejuni which can lead to diarrhoeal disease. |
