AUTHOR=Zhang Tingting , Wei Xianxian , Li Yijie , Huang Shuai , Wu Yulin , Cai Shanshan , Aipire Adila , Li Jinyao 

TITLE=Dendritic cell-based vaccine prepared with recombinant Lactococcus lactis enhances antigen cross-presentation and antitumor efficacy through ROS production

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1208349

DOI=10.3389/fimmu.2023.1208349

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p><italic>Lactococcus lactis</italic> (<italic>L.L</italic>) is safe and can be used as vehicle. In this study, the immunoregulatory effect of <italic>L.L</italic> on dendritic cell (DC) activation and mechanism were investigated. The immune responses and antigen cross-presentation mechanism of DC-based vaccine prepared with OVA recombinant <italic>L.L</italic> were explored.</p></sec><sec><title>Methods</title><p>Confocal microscopy and flow cytometry were used to analyze the mechanism of <italic>L.L</italic> promoting DC maturation, phagosome membrane rupture and antigen presentation. The antitumor effect of DC vaccine prepared with <italic>L.L-OVA</italic> was assessed in the B16-OVA tumor mouse model.</p></sec><sec><title>Results</title><p><italic>L.L</italic> significantly promoted DC maturation, which was partially dependent on TLR2 and downstream MAPK and NF-κB signaling pathways. <italic>L.L</italic> was internalized into DCs by endocytosis and did not co-localized with lysosome. OVA recombinant <italic>L.L</italic> enhanced antigen cross-presentation of DCs through the phagosome-to-cytosol pathway in a reactive oxygen species (ROS)- and proteasome-dependent manner. In mouse experiments, <italic>L.L</italic> increased the migration of DCs to draining lymph node and DC vaccine prepared with OVA recombinant <italic>L.L</italic> induced strong antigen-specific Th1 and cytotoxic T lymphocyte responses, which significantly inhibited B16-OVA tumor growth.</p></sec><sec><title>Conclusion</title><p>This study demonstrated that recombinant <italic>L.L</italic> as an antigen delivery system prepared DC vaccine can enhance the antigen cross-presentation and antitumor efficacy.</p></sec>