Recombinant *Lactococcus lactis* expressing IFN-γ alleviates viral enteritis in mice via microbial and metabolic modulation
Background
Viral enteritis significantly impacts the animal industry, causing substantial economic losses. Current preventive and therapeutic strategies, including vaccines and antibiotics, face limitations due to rapid virus mutation, increasing drug resistance, and undesirable side effects. This creates a critical need for novel, effective, and safe interventions. Interferon-gamma (IFN-γ) is a potent cytokine known for its antiviral and immunomodulatory properties. Leveraging food-grade lactic acid bacteria (LAB) as a delivery system for therapeutic proteins like IFN-γ offers a promising approach, combining probiotic benefits with targeted immunomodulation to address the gaps in current viral enteritis management.
Study Design
Researchers developed an edible lactic acid bacteria (LAB) delivery system using a recombinant Lactococcus lactis strain, pNZ8149-IFN-γ/NZ3900, engineered to express interferon-gamma (IFN-γ) via a nisin-inducible (NICE) system for active IFN-γ release. The therapeutic potential was evaluated in a mouse model of viral enteritis and further investigated using intestinal organoid coculture experiments. An acute virulence test was conducted to confirm the strain's safety. The study assessed primary endpoints including intestinal inflammation, tissue damage, and serum inflammatory factors. Organoid experiments specifically tested the recombinant LAB's ability to resist Poly(I:C)-induced inflammation and damage.
Results
The recombinant Lactococcus lactis strain expressing IFN-γ demonstrated significant therapeutic efficacy in the mouse viral enteritis model. It was shown to significantly alleviate intestinal inflammation and tissue damage. Furthermore, the treatment led to a reduction in serum inflammatory factors, indicating a systemic immunomodulatory effect. An acute virulence test confirmed the safety of the recombinant strain, showing no adverse effects. At the organoid level, the recombinant LAB effectively resisted Poly(I:C)-induced inflammation and damage, mirroring the in vivo findings. This suggests a direct protective effect on intestinal cells. The study highlights the first successful combination of IFN-γ with food-grade LAB for oral delivery and targeted immunomodulation. > The recombinant Lactococcus lactis strain significantly alleviated intestinal inflammation and tissue damage and reduced serum inflammatory factors in a mouse viral enteritis model.
Key Findings
- Recombinant Lactococcus lactis expressing IFN-γ was successfully constructed for oral delivery.
- The strain significantly alleviated intestinal inflammation and tissue damage in a mouse viral enteritis model.
- Treatment with the recombinant LAB led to a reduction in serum inflammatory factors.
- The recombinant LAB resisted
Poly(I:C)-induced inflammation and damage in intestinal organoids. - An acute virulence test confirmed the safety of the recombinant Lactococcus lactis strain.
Why It Matters
This research introduces a groundbreaking, antibiotic-free strategy for preventing and treating viral enteritis, particularly relevant for the animal industry. By combining the probiotic benefits of Lactococcus lactis with the potent antiviral and immunomodulatory effects of IFN-γ, this oral delivery system offers a dual-action therapeutic. The practical takeaway is a novel, safe, and potentially highly effective oral intervention that could reduce reliance on conventional antibiotics and vaccines, mitigating issues like drug resistance and viral mutation. While currently preclinical, this approach paves the way for future development of edible, targeted immunotherapies, potentially simplifying administration and improving animal welfare and productivity. Further research is needed to translate this into a usable protocol for livestock, including optimal dosing and frequency.
lactococcus lactis
ifn-gamma
viral enteritis
immunomodulation
probiotic
animal study
