<i>LigiLactobacillus saerimneri</i> M-11 as a Promising Mucosal Delivery Vector for Chickens: Genomic Insights and Discriminative Modulation of Dendritic Cell Activation.

Abstract

<i>LigiLactobacillus saerimneri</i> (<i>L. sae</i>) has shown considerable promise as a probiotic in recent years, particularly in poultry production. Comprehensive evaluation of its genetic functions, safety profile, and immunogenicity is essential prior to practical application. Our previous study demonstrated that the chicken-derived strain <i>L. sae</i> M-11 colonizes effectively and exhibits a favorable safety profile at adequate dosages. In this study, we further evaluated the potential of <i>L. sae</i> M-11 by analyzing its genetic basis for intestinal adaptation, metabolic features, safety risks, and suitability as a delivery vector. Comparative genomic analysis revealed that <i>L. sae</i> has evolved distinctive genetic features and functional specialization that may facilitate host adaptation. Genomic stability assessments and virulence factor screening confirmed that <i>L. sae</i> M-11 poses no substantial health risks. Furthermore, based on transmembrane protein predictions, the LPQTGE-motif protein was identified as a cell wall anchor in genetically engineered <i>L. sae</i> M-11 using immunoelectron microscopy. Notably, this delivery system selectively activated peripheral blood monocyte-derived dendritic cells (PB-MoDCs) in vitro, as evidenced by the up-regulation of maturation markers (CD83, CD80), pro-inflammatory cytokines (IL-1β, IL-6), Th1-associated IL-12, and the chemokine CXCLi1. However, it exhibited a limited antigen presentation capacity, indicated by low expression levels of CD40, MHCII, DEC205, TNF-α, and IFN-γ. The prospects and challenges associated with the application of <i>L. sae</i> M-11 have been discussed. Overall, these findings support the potential development of <i>L. sae</i> M-11 as a microbial cell factory and mucosal delivery vector.