Lipoproteins from Bilophila wadsworthia cell wall induce innate immune responses through Toll-like receptor 2

Abstract

Objectives

Bilophila wadsworthia is a commensal gram-negative anaerobic bacterium in the human gut that is often isolated from patients diagnosed with appendicitis and inflammatory bowel disease. Although previous studies have indicated that B. wadsworthia can cause and/or exacerbate inflammatory diseases, the precise underlying mechanism remains unclear. In the present study, we explored the inflammation-causing virulence factors of B. wadsworthia.

Methods

To identify the virulence factors of B. wadsworthia, we investigated the whole-genome sequences of 25 B. wadsworthia isolates. We then used the publicly available virulence factor database (VFDB) to search for virulence factor genes. We also conducted in vitro and in vivo studies to determine the importance of the selected virulence factors causing inflammation.

Results

Bilophila wadsworthia isolates have 30 common virulence factor genes that contribute to inflammation, invasion of the human body, and effector delivery system. These genes were associated with lipopolysaccharide, capsules, and membrane-associated proteins. Among them, lipoproteins, sometimes act as components of transporter proteins in the bacterial cell wall, upregulated the expression of tumor necrosis factor in murine spleen cells. However, the effect of lipoproteins was attenuated by a Toll-like receptor 2 antagonist. Additionally, orally administered B. wadsworthia and B. wadsworthia-produced lipoproteins worsened colitis in vivo.

Conclusions

Bilophila wadsworthia contains genes that encode various virulence factors. Among these, lipoproteins produced by B. wadsworthia can act as inflammation-inducing factors via Toll-like receptor 2.