Construction of recombinant Lactococcus expressing thymosin and interferon fusion protein and its application as an immune adjuvant.

Microbial cell factories2024PMID: 38321474

View on PubMed DOI: 10.1186/s12934-024-02308-1

Plain Language Summary

Scientists created a genetically engineered food-safe bacterium (Lactococcus lactis) that produces a combined thymosin alpha-1 and chicken interferon protein. When tested, this recombinant bacterium activated immune signaling pathways, boosted immune cell responses, improved gut bacteria composition, and enhanced vaccine effectiveness in chickens. This approach could lead to the development of natural, food-safe immune boosters for animal health.

Abstract

BACKGROUND: In recent years, biosafety and green food safety standards have increased the demand for immune enhancers and adjuvants. In the present study, recombinant food-grade Lactococcus lactis (r-L. lactis-Tα1-IFN) expressing thymosin Tα1 and chicken interferon fusion protein was constructed. RESULTS: The in vitro interactions with macrophages revealed a mixture of recombinant r-L. lactis-Tα1-IFN could significantly activate both macrophage J774-Dual™ NF-κB and interferon regulator (IRF) signaling pathways. In vitro interactions with chicken peripheral blood mononuclear cells (PBMCs) demonstrated that a mixture of recombinant r-L. lactis-Tα1-IFN significantly enhanced the expression levels of interferon (IFN)-γ, interleukin (IL)-10, CD80, and CD86 proteins in chicken PBMCs. Animal experiments displayed that injecting a lysis mixture of recombinant r-L. lactis-Tα1-IFN could significantly activate the proliferation of T cells and antigen-presenting cells in chicken PBMCs. Moreover, 16S analysis of intestinal microbiota demonstrated that injection of the lysis mixture of recombinant r-L. lactis-Tα1-IFN could significantly improve the structure and composition of chicken intestinal microbiota, with a significant increase in probiotic genera, such as Lactobacillus spp. Results of animal experiments using the lysis mixture of recombinant r-L. lactis-Tα1-IFN as an immune adjuvant for inactivated chicken Newcastle disease vaccine showed that the serum antibody titers of the experimental group were significantly higher than those of the vaccine control group, and the expression levels of cytokines IFN-γ and IL-2 were significantly higher than those of the vaccine control group. CONCLUSION: These results indicate that food-safe recombinant r-L. lactis-Tα1-IFN has potential as a vaccine immune booster and immune adjuvant. This study lays the foundation for the development of natural green novel animal immune booster or immune adjuvant.

Authors

Liu, Zengqi; Zhang, Suhua; Hu, Hongjiao; Wang, He; Qiu, Yu; Dong, Mingqi; Wang, Muping; Cui, Ziyang; Cui, Hongyu; Wang, Yunfeng; He, Gaoming

Keywords

Immune adjuvantImmune enhancerInterferonRecombinant LactococcusThymosin