Lawsonia intracellularis regulates nuclear factor-κB signalling pathway during infection.
Authors: Yang Huan W, Hu Tuanjun, Ait-Ali Tahar
Journal: PloS one
Summary
# Editorial Summary Lawsonia intracellularis, the causative agent of proliferative enteropathy in horses and other mammals, triggers a coordinated innate immune response centred on nuclear factor-κB (NF-κB) signalling during infection. Researchers compared how pig kidney cells responded to both a virulent clinical strain (Dkp23) and a live-attenuated vaccine strain (Enterisol) by measuring NF-κB activation, cytokine expression, and bacterial load over a five-day infection period. Peak bacterial load coincided with robust NF-κB activation at day 5 post-infection, characterised by p65 phosphorylation and nuclear translocation, alongside significant upregulation of pro-inflammatory cytokines including TNF-α, IFN-γ, IL-6 and IL-8—responses that were particularly pronounced in vaccine-strain infected cells and correlated with reduced cell viability. Whilst both strains induced comparable NF-κB signalling intensity, the vaccine strain generated moderately higher cytokine expression relative to bacterial load, potentially reflecting its attenuated replication capacity. For equine practitioners, these findings illuminate how the horse's gut epithelium mounts a threshold-dependent immune response to L. intracellularis, with implications for understanding vaccination efficacy and the inflammatory tissue damage characteristic of clinical proliferative enteropathy.
Read the full abstract on PubMed
Practical Takeaways
- •Understanding how L. intracellularis manipulates immune signalling may inform development of more effective vaccines and therapeutic interventions for proliferative enteropathy in horses
- •The differential immune response between vaccine and field strains suggests vaccine efficacy may depend on the strength of NF-κB pathway activation
- •In-vitro findings provide mechanistic basis for future in-vivo studies to validate immune responses and optimise treatment strategies for equine proliferative enteropathy
Key Findings
- •NF-κB signalling pathway is significantly activated at 5 days post-infection when L. intracellularis bacterial load peaks
- •Pro-inflammatory cytokines TNF-α, IFN-γ, IL-6 and IL-8 expression is induced during L. intracellularis infection, correlating with bacterial load
- •Live-attenuated Enterisol vaccine strain triggers higher NF-κB activation and greater reduction in cell viability compared to clinical strain Dkp23
- •NF-κB signalling induction directly correlates with intracellular bacterial load in infected cells