Related Experiment Video
Updated: Feb 9, 2026
Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity
Published on: June 14, 2024
Monocyte Response to Different Campylobacter jejuni Lysates Involves Endoplasmic Reticulum Stress and the
Barbara Canonico1, Gianna Di Sario2, Erica Cesarini3
1Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy. barbara.canonico@uniurb.it.
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.
Insights
Campylobacter jejuni cytolethal distending toxin (CDT) affects mitochondria and lysosomes in human monocytes. CDT induces cell cycle arrest and lysosomal changes, potentially promoting resistance to apoptosis.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Campylobacter jejuni is a common cause of human gastroenteritis.
- The cytolethal distending toxin (CDT) is a key virulence factor of C. jejuni.
- C. jejuni infection can lead to Guillain-Barré Syndrome, possibly mediated by CDT.
Purpose of the Study:
- To investigate the effects of C. jejuni lysates from different strains on human monocytes.
- To determine the specific cellular targets of C. jejuni virulence factors, including CDT.
- To elucidate the role of CDT in C. jejuni-induced cell death and inflammatory responses.
Main Methods:
- Analysis of C. jejuni lysates from various strains.
- Treatment of donor monocytes with bacterial lysates.
- Cytometric and confocal microscopy analyses to assess cellular damage.
- Evaluation of mitochondrial and lysosomal alterations.
- Assessment of endoplasmic reticulum (ER) stress and cytosolic Ca2+ levels.
- Monitoring of p53 expression.
Main Results:
- Different C. jejuni strains induced distinct cellular responses: ATCC 33291 primarily caused mitochondrial alterations, indicating intrinsic apoptosis.
- The ISS 1 wild-type strain predominantly induced lysosomal alterations.
- All C. jejuni lysates induced ER stress and increased cytosolic Ca2+ content, suggesting roles for non-CDT virulence factors.
- CDT was primarily responsible for changes in lysosomal compartments and p53 expression.
- Loss of p53, linked to CDT, may confer resistance to apoptosis.
Conclusions:
- C. jejuni employs different virulence factors to target distinct cellular organelles in monocytes.
- CDT plays a significant role in C. jejuni pathogenesis by inducing lysosomal damage and affecting p53, potentially promoting cell survival.
- ER stress is induced by factors other than CDT in C. jejuni infections.
Related Concept Videos
01:39Endoplasmic Reticulum
01:43The Endoplasmic Reticulum
01:21Smooth Endoplasmic Reticulum
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
01:34Directing Proteins to the Rough Endoplasmic Reticulum
02:45Responses to Heat and Cold Stress
02:02Responses to Salt Stress