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Toxins 2018, 10(6), 239; https://doi.org/10.3390/toxins10060239

Monocyte Response to Different Campylobacter jejuni Lysates Involves Endoplasmic Reticulum Stress and the Lysosomal–Mitochondrial Axis: When Cell Death Is Better Than Cell Survival

Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
These authors contributed equally to this work.
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Received: 3 May 2018 / Revised: 6 June 2018 / Accepted: 11 June 2018 / Published: 13 June 2018
(This article belongs to the Section Bacterial Toxins)
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Abstract

Campylobacter jejuni is a Gram-negative spiral-shaped bacterium, commonly associated with gastroenteritis in humans. It explicates its virulence also by the cytolethal distending toxin (CDT), able to cause irreversible cell cycle arrest. Infection by C. jejuni may result in the development of the Guillain–Barré Syndrome, an acute peripheral neuropathy. Symptoms of this disease could be caused by CDT-induced cell death and a subsequent inflammatory response. We tested C. jejuni lysates from different strains on donor monocytes: in fact, monocytes are potent producers of both pro- and anti-inflammatory cytokines, playing a major role in innate immunity and in non-specific host responses. We found, by cytometric and confocal analyses, that mitochondria and lysosomes were differently targeted: The C. jejuni strain that induced the most relevant mitochondrial alterations was the ATCC 33291, confirming an intrinsic apoptotic pathway, whereas the C. jejuni ISS 1 wild-type strain mostly induced lysosomal alterations. Lysates from all strains induced endoplasmic reticulum (ER) stress in monocytes, suggesting that ER stress was not associated with CDT but to other C. jejuni virulence factors. The ER data were consistent with an increase in cytosolic Ca2+ content induced by the lysates. On the contrary, the changes in lysosomal acidic compartments and p53 expression (occurring together from time 0, T0, to 24 h) were mainly due to CDT. The loss of p53 may prevent or impede cell death and it was not observable with the mutant strain. CDT not only was responsible for specific death effects but also seemed to promote an apoptotic stimuli-resisting pathway. View Full-Text
Keywords: Campylobacter jejuni; apoptosis; sub-lethal effect; lysosome; mitochondria Campylobacter jejuni; apoptosis; sub-lethal effect; lysosome; mitochondria
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Canonico, B.; Di Sario, G.; Cesarini, E.; Campana, R.; Luchetti, F.; Zamai, L.; Ortolani, C.; Nasoni, M.G.; Baffone, W.; Papa, S. Monocyte Response to Different Campylobacter jejuni Lysates Involves Endoplasmic Reticulum Stress and the Lysosomal–Mitochondrial Axis: When Cell Death Is Better Than Cell Survival. Toxins 2018, 10, 239.

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