ORIGINAL RESEARCH article
Front. Immunol.
Sec. Microbial Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1624092
This article is part of the Research TopicAdvances in Immunity and Microbiome: Exploring Key Interactions and InnovationsView all 9 articles
SFB flagellin mediates cell adhesion, endocytosis and immune regulation in germ-free mice
Provisionally accepted
- 1Guangxi University, Nanning, China
- 2Guangxi Academy of Sciences, Nanning, China
- 3Guangxi Veterinary Research Institute, Nanning, China
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The colonization dynamics of segmented filamentous bacteria (SFB) play a pivotal role in host immune regulation. To investigate the functions of SFB flagellin in bacterial adhesion, cellular internalization, and immune modulation, we engineered Lactococcus lactis to express murine and rat SFB flagellin genes (Lac-mfliC3 and Lac-rfliC3). In vitro co-culture experiments with intestinal epithelial cell lines (MODE-K and IEC-18) demonstrated significantly improved bacterial adhesion capabilities mediated by SFB flagellin. Germ-free mouse colonization assays revealed prolonged fecal persistence of flagellin-expressing strains. Immunohistochemical analysis of ileal tissues showed colocalization of recombinant bacteria with the lysosomal-associated membrane protein 2 (Lamp2), confirming cellular internalization. Furthermore, mfliC3-expressing Escherichia coli exhibited active invasion into MODE-K cells. RNA sequencing analysis identified significant enrichment of Th17 cell differentiation pathways in both ileum and hepatic tissues from Lac-rfliC3-colonized mice. Correspondingly, the Lac-mfliC3 group showed elevated serum levels of Th17-associated cytokines including IFN-γ, IL-23p19, IL-17A, IL-5, and IL-6 compared to controls. Molecular docking simulations revealed high-affinity interactions between SFB flagellins and endocytic regulators endophilin A2 and αM integrin. These results demonstrate that SFB flagellin mediates bacterialepithelial interactions through dual mechanisms of adhesion potentiation and active internalization, ultimately driving Th17-mediated immune responses.
Keywords: segmented filamentous bacteria, Flagellin, Germ-free mouse, Bacterial Adhesion, Endocytosis, Th17 cell differentiation
Received: 07 May 2025; Accepted: 28 Jul 2025.
Copyright: © 2025 Yin, Chen, Wu, Cao, Li, Zhu, Li, Wei and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yeshi Yin, Guangxi University, Nanning, China
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