Lactobacillus plantarum surface-displayed FomA (Fusobacterium nucleatum) protein generally stimulates protective immune responses in mice

Xiaoyu Zhang; Huijie Xiao; Huaiyu Zhang; Yang Jiang

doi:10.3389/fmicb.2023.1228857

Lactobacillus plantarum surface-displayed FomA (Fusobacterium nucleatum) protein generally stimulates protective immune responses in mice

Front Microbiol. 2023 Sep 20:14:1228857. doi: 10.3389/fmicb.2023.1228857. eCollection 2023.

Authors

Xiaoyu Zhang¹, Huijie Xiao¹, Huaiyu Zhang², Yang Jiang¹

Affiliations

¹ Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
² Department of Rehabilitation Medicine, China-Japan Union Hospital of Jilin University, Changchun, China.

Abstract

A significant correlation is observed between Fusobacterium nucleatum (F. nucleatum) and the evolution of inflammatory bowel disease (IBD). Particularly, FomA, a critical pathogenic element of F. nucleatum, inflicts substantial detriment to human intestinal health. Our research focused on the development of recombinant Lactobacillus plantarum that expresses FomA protein, demonstrating its potential in protecting mice from severe IBD induced by F. nucleatum. To commence, two recombinant strains, namely L. plantarum NC8-pSIP409-pgsA'-FomA and NC8-pSIP409-FnBPA-pgsA'-FomA, were successfully developed. Validation of the results was achieved through flow cytometry, ELISA, and MTT assays. It was observed that recombinant L. plantarum instigated mouse-specific humoral immunity and elicited mucosal and T cell-mediated immune responses. Significantly, it amplified the immune reaction of B cells and CD4⁺T cells, facilitated the secretion of cytokines such as IgA, IL4, and IL10, and induced lymphocyte proliferation in response to FomA protein stimulation. Finally, we discovered that administering recombinant L. plantarum could protect mice from severe IBD triggered by F. nucleatum, subsequently reducing pathological alterations and inflammatory responses. These empirical findings further the study of an innovative oral recombinant Lactobacillus vaccine.

Keywords: F. nucleatum; FomA; IBD; L. plantarum; recombinant.

Grants and funding

This study was supported by the Natural Science Foundation of Jilin Province (20200201430JC to YJ) and the Jilin Province Development and Reform Commission Project (2021C043-9 to YJ).