Campylobacter jejuni Modulates Reactive Oxygen Species Production and NADPH Oxidase 1 Expression in Human Intestinal Epithelial Cells

Abstract

Campylobacter jejuni is the major bacterial cause of foodborne gastroenteritis worldwide. Mechanistically, how this pathogen interacts with intrinsic defence machinery of human intestinal epithelial cells (IECs) remains elusive. To address this, we investigated how C. jejuni counteracts the intracellular and extracellular reactive oxygen species (ROS) in IECs. Our work shows that C. jejuni differentially regulates intracellular and extracellular ROS production in human T84 and Caco-2 cells. C. jejuni downregulates the transcription and translation of nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase (NOX1), a key ROS-generating enzyme in IECs and antioxidant defence genes CAT and SOD1. Furthermore, inhibition of NOX1 by diphenylene iodonium (DPI) and siRNA reduced C. jejuni ability to interact, invade, and intracellularly survive within T84 and Caco-2 cells. Collectively, these findings provide mechanistic insight into how C. jejuni modulates the IEC defence machinery.

Effect of the polysaccharide capsule and its heptose on the resistance of Campylobacter jejuni to innate immune defenses

“…The dampening seemed more efficient in human cells (~2/3 of the basal ROS levels) than in chicken macrophages (~half only). Mirroring these data, other C. jejuni strains also moderated ROS induction in human intestinal epithelial cells (Hong et al, 2023 ) and the reduction was linked to decreased transcription of Nox1. Our H 2 O 2 exposure data showed that C. jejuni is not overly sensitive to short‐term and limited oxidative stress and that the capsule and the heptose only provide limited protection.…”

Exploring the Contribution of Campylobacter jejuni to Post-Infectious Irritable Bowel Syndrome: A Literature Review

“…This section delves into the specific disruptions induced by C. jejuni, including increased intestinal permeability, immune system dysregulation and their consequential roles in the pathogenesis of PI-IBS. Upon attachment and invasion into human intestinal epithelial cells (IECs), C. jejuni manipulates the host's cytoskeletal regulation to optimize its invasive capabilities [31]. After successfully invading, C. jejuni is found within cytoplasmic compartments termed Campylobacter-containing vacuoles (CCVs) [31].…”

“…Upon attachment and invasion into human intestinal epithelial cells (IECs), C. jejuni manipulates the host's cytoskeletal regulation to optimize its invasive capabilities [31]. After successfully invading, C. jejuni is found within cytoplasmic compartments termed Campylobacter-containing vacuoles (CCVs) [31]. Pathogens' virulence factors can compromise the epithelial barrier and enhance intestinal permeability by activating myosin light-chain kinase, which facilitates the degradation of tight junction (TJ) proteins, disrupts actin functionality and triggers apoptosis in intestinal epithelial cells (IECs).…”